Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a...Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.展开更多
Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well esta...Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.展开更多
In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism...In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism is not clear.This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism.The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(HCG).Then the rats were randomly divided into model group(M),Shoutai pills group(S),progesterone group(P)and normal group(N).All the pregnant rats were treated from the first day.The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively,and N and M groups were given the same volume of normal saline and distilled water respectively.After treatment for 7 days,the animals were executed for serum and uterine tissues.The ELISA method was adopted to detect the contents of Thl cytokines[interferon-γ(INF-γ),interleukin-2(IL-2)]and Th2 cytokines(IL-4,IL-6,IL-10).The expression of leukemia inhibitory factor(L1F)and leukemia inhibitory factor receptor(LIFR)was detected by Western blotting and real-time PCR.As compared with N group,the expression levels of IFN-y and IL-2 in M group were significantly increased,and those of IL-4,IL-6,IL-10.LIF and LIFR were significantly decreased(P<0.05).As compared with M group,the levels of IL-4,IL-6,IL-10,LIF and LIFR in S group were significantly increased(P<0.05),and those of IFN-γand IL-2 were significantly decreased(P<0.05).It was suggested that Shoutai pills can increase the levels of IL-4.1L-6,IL-10,LIF and LIFR as well as reduce the levels of INF-γand IL-2 in rats with stimulated ovulation.The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balanee of Th1/Th2 cytokines.展开更多
Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC ...Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.展开更多
Selenium (Se) is an essential trace element. Autoimmune thyroid diseases (AITD) are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the ...Selenium (Se) is an essential trace element. Autoimmune thyroid diseases (AITD) are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium (Se) and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases (AITD).展开更多
Coronavirus disease 2019(COVID-19)is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2(SARS-CoV-2)that is associated with a high spreading and mortality rate...Coronavirus disease 2019(COVID-19)is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2(SARS-CoV-2)that is associated with a high spreading and mortality rate.On the date this review was written,SARS-CoV-2 infected about 96 million people and killed about 2 million people.Several arguments disclosed the high mortality of COVID-19 due to acute respiratory distress syndrome or change in the amount of angiotensin-converting enzyme 2(ACE2)receptor expression or cytokine storm strength production.In a similar pattern,hepatic impairment patients co-infected with SARS-CoV-2 exhibited overexpression of ACE2 receptors and cytokine storm overwhelming,which worsens the hepatic impairment and increases the mortality rate.In this review,the impact of SARS-CoV-2 on hepatic impairment conditions we overviewed.Besides,we focused on the recent studies that indicated cytokine storm as well as ACE2 as the main factors for high COVID-19 spreading and mortality while hinting at the potential therapeutic strategies.展开更多
BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice dr...BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.展开更多
Liopxin A4(LXA4) is considered to be a crucial modulator in the inflammatory responses. In the present study, we aimed to study the effect of LXA4 on the inflammatory cytokines production induced by lipopolysacchar...Liopxin A4(LXA4) is considered to be a crucial modulator in the inflammatory responses. In the present study, we aimed to study the effect of LXA4 on the inflammatory cytokines production induced by lipopolysaccharide(LPS) and the possible mechanism in normal human epidermal keratinocytes(NHEKs). NHEKs were isolated and cultured. The expression of toll-like receptor 4(TLR4), LXA4 receptor(ALXR) and aryl hydrocarbon receptor(Ah R) in NHEKs was detected by reverse transcription polymerase chain reaction(RT-PCR). The m RNA and protein levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1β(IL-1β) were determined in NHEKs stimulated by LPS(10 μg/m L) with or without preincubation with LXA4(100 nmol/L) for 30 min by real-time quantitative PCR(real-time q PCR) and enzyme-linked immunosorbent assay(ELISA), respectively. The expression levels of tumor necrosis factor receptor-associated factor 6(TRAF6) and suppressors of cytokine signaling 2(SOCS2) m RNAs and proteins, and nuclear translocation of NF-k B-p65 were measured by real-time q PCR and Western blotting, respectively. The results showed that NHEKs expressed TLR4, ALXR and Ah R. LXA4 significantly inhibited the m RNA and protein expression levels of TNF-α, IL-1β and TRAF6 induced by LPS in NHEKs, and LXA4 obviously increased the expression of SOCS2 at m RNA and protein levels. The nuclear NF-k B-p65 protein expression induced by LPS was inhibited after preincubation with LXA4 in NHEKs. It was concluded that LXA4 inhibits the LPS-induced production of TNF-α and IL-1β in NHEKs by up-regulating SOCS2 and down-regulating TRAF6.展开更多
In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of ...In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animals were pretreated with estradiol. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-2, IL-4, IL-10 and TGF-β1 in the vagina in the mice of different groups at different time points after the beginning of the experiment. The average expression level of IL-2 mRNA in group D (estrogen-treated mice) was significantly higher than that in groups H (estrogen-untreated mice) and I (control group) on the day 2. The average expression level of IL-4 mRNA in group D was significantly higher than that in groups I and H on the day 5. The average expression level of IL-10 mRNA in group D was significantly higher than that in groups H and I from day 7 to 11. The average expression level of TGF-β1 mRNA in group D was significantly higher than that in groups H and I at all time points. It was concludes that the high-level expression of IL-2 mRNA during early infection was associated with clearance of mucosal C. albicans, and the high-level expression of IL-10 mRNA during late stage of the infection was related to susceptibility to infection. TGF-β1 may play a predominant role when the virtual absence of changes in other Th-type cytokines during infection.展开更多
目的探索初治慢性乙型肝炎(CHB)患者血清中细胞因子表达水平及其与病毒载量和肝脏炎症程度的关系,以期为临床动态评估CHB的病情和预后提供新思路。方法选择2018年10月至2019年11月就诊于海军军医大学(第二军医大学)第一附属医院感染科...目的探索初治慢性乙型肝炎(CHB)患者血清中细胞因子表达水平及其与病毒载量和肝脏炎症程度的关系,以期为临床动态评估CHB的病情和预后提供新思路。方法选择2018年10月至2019年11月就诊于海军军医大学(第二军医大学)第一附属医院感染科的初治慢性乙型肝炎病毒(HBV)感染者68例,健康对照者12名,通过ELISA检测血清中细胞因子IL-17A、IL-2、IL-21和IL-4表达水平,化学发光法检测HBV血清学标志物,qPCR法检测血清HBV DNA定量,全自动生化分析仪检测肝功能指标。采用Spearman相关分析评估血清细胞因子与病毒载量及肝脏炎症程度的相关性,绘制ROC曲线评价血清细胞因子水平对肝脏炎症程度的判断效能。结果相较于健康对照者,初治CHB患者血清IL-17A[17.50(11.99,25.36)pg/mL vs 13.74(9.07,16.94)pg/mL,Z=-2.001,P=0.045]、IL-21[37.12(23.85,77.66)pg/mL vs 20.30(17.90,24.19)pg/mL,Z=-3.485,P<0.01]水平升高,IL-2[57.19(31.10,79.92)pg/mL vs 73.06(62.41,105.84)pg/mL,Z=-2.509,P=0.012]水平降低,IL-4[11.40(5.79,18.62)pg/mL vs 10.84(8.05,25.20)pg/mL,Z=-0.681,P=0.496]水平差异无统计学意义。不同病程CHB患者的IL-17A表达水平差异有统计意义(H=8.870,P=0.031)。与非活动状态患者相比,炎症活动状态CHB患者血清中IL-17A[17.71(12.25,27.92)pg/mL vs 16.51(6.29,20.22)pg/mL]和IL-21[39.29(24.71,83.19)pg/mL vs 25.06(19.37,49.43)pg/mL]水平升高、IL-2[57.19(31.10,77.68)pg/mL vs 71.24(48.07,117.39)pg/mL]水平下降(均P<0.05),IL-4[11.40(5.94,18.12)pg/mL vs 14.57(3.12,24.49)pg/mL]水平差异无统计学意义(P>0.05)。HBeAg阳性CHB患者、HBeAg阴性CHB患者血清IL-17A[15.34(10.65,25.04)、19.98(15.55,34.14)pg/mL vs 13.74(9.07,16.94)pg/mL,H=10.061,P=0.007]和IL-21[37.74(25.06,82.87)、51.74(23.32,83.82)pg/mL vs 20.30(17.90,24.19)pg/mL,H=12.444,P=0.002]水平高于健康对照者,IL-2[57.19(37.45,79.92)、37.45(18.32,73.06)pg/mL vs 73.06(62.41,105.84)pg/mL,H=6.576,P=0.037]水平低于健康对照者。初治CHB患者血清IL-17A、IL-21、IL-4水平与HBV DNA定量无相关性(r=0.02、0.23、0.07,均P>0.05),IL-2水平与HBV DNA定量存在弱相关性(r=0.32,P=0.01)。初治CHB患者血清IL-17A、IL-21水平与丙氨酸转氨酶(ALT)水平(r=0.59、0.49,均P<0.01)和天冬氨酸转氨酶(AST)水平(r=0.47、0.36,均P<0.01)均存在相关性,而IL-2、IL-4水平与ALT、AST水平均无相关性(均P>0.05)。ALT≥300 U/L初治CHB组、ALT<300 U/L初治CHB组及健康对照组间血清IL-17A、IL-2、IL-21水平差异有统计学意义(均P<0.05),其中ALT≥300 U/L初治CHB组IL-17A、IL-21水平均高于ALT<300 U/L初治CHB组及健康对照组(均P<0.01),ALT<300 U/L初治CHB组IL-2水平低于健康对照组、IL-21水平高于健康对照组(均P<0.01)。ROC曲线分析结果显示,IL-17A判断肝脏炎症程度的AUC值为0.8933(95%CI 0.7930~0.9936),IL-21判断肝脏炎症程度的AUC值为0.7600(95%CI 0.6227~0.8973)。结论IL-17A、IL-2和IL-21参与慢性HBV感染进程。初治CHB患者无论HBeAg阳性与否或炎症程度高低,血清IL-17A和IL-21水平均升高,IL-2水平均下降;IL-2与HBV DNA定量有一定相关性;IL-17A和IL-21与ALT及AST均存在正相关;检测IL-17A和IL-2有助于病情评估与预后判断。展开更多
Objective:To assess the association between genetic variants of transferrin receptor 2(TFR2)exon 4 and anemia status and to describe the expression levels of several cytokines,hepcidin,soluble transferrin receptor and...Objective:To assess the association between genetic variants of transferrin receptor 2(TFR2)exon 4 and anemia status and to describe the expression levels of several cytokines,hepcidin,soluble transferrin receptor and erythropoietin.Methods:Institutional based comparative study was done randomly to recruit 106 pregnant women who attended antenatal care in three different health centers in Boyolali Regency,Central Java from May 2015 to September 2015.DNA was extracted from peripheral blood samples of selected pregnant women and sequencing was done for TFR2 exon 4.Furthermore,enzyme-linked immunosorbent assay was conducted to measure the expression levels of interleukin 6,interleukin 4,transforming growth factorβand iron-metabolism related proteins such as hepcidin,soluble transferrin receptor,and erythropoietin.Gene alignment was performed by using a CLUSTAL W program.Collected data were analyzed statistically by using parametric and nonparametric tests with Statistical Product and Service Solutions(SPSS)20.0 for Windows.Results:Three novel genetic variants from TFR2 exon 4(position 603,605 and 606)were associated with anemia status.Moreover,the expression levels of interleukin 6,interleukin 4,transforming growth factorβand erythropoietin were higher in anemic pregnant women than those of nonanemic pregnant women but only erythropoietin level reached statistical significance.These results were followed by decreases of hepcidin and soluble transferrin receptor levels.Conclusions:Various factors contribute to anemia prevalence among pregnant women in Boyoali Regency,Central Java,Indonesia.Our novel findings showed that TFR2 exon 4 has 3 mutational sites in position 603,605 and 606.These novel genetic variants may provide a new insight into the role of TFR2 in anemia.展开更多
With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune respon...With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.展开更多
Objective Paroxysmal kinesigenic dyskinesia(PKD)is a rare movement disorder PRRT2 gene mutations have been reported to cause PKD.However,the pathophysiological mechanism of PKD remains unclear,and it is unknown whethe...Objective Paroxysmal kinesigenic dyskinesia(PKD)is a rare movement disorder PRRT2 gene mutations have been reported to cause PKD.However,the pathophysiological mechanism of PKD remains unclear,and it is unknown whether an inflammatory response is involved in the occurrence of this disease.We aimed to investigate the symptomatology,genotype,and serum cytokines of patients with PKD.Methods We recruited 21 patients with PKD,including 7 with familial PKD and 14 with sporadic PKD.Their clinical features were investigated,and blood samples were collected,and PRRT2 mutations and cytokine levels were detected.Results The mean age at PKD onset was 12.3±2.2 years old.Dystonia was the most common manifestation of dyskinesia,and the limbs were the most commonly affected parts.All attacks were induced by identifiable kinesigenic triggers,and the attack durations were brief(<1 min).Four different mutations from 9 probands were identified in 7 familial cases(71.4%)and 14 sporadic cases(28.6%).Two of these mutations(c.649dupC,c.620_621delAA)had already been reported,while other 2(c.1018_1019delAA,c.1012+1G>A)were previously undocumented.The tumor necrosis factor(TNF)-αlevel in the PKD group was significantly higher than that in the age-and sex-matched control group(P=0.025).There were no significant differences in the interleukin(IL)-1β,IL-2R,IL-6,IL-8,or IL-10 levels between the two groups.Conclusion In this study,we summarized the clinical and genetic characteristics of PKD.We found that the serum TNF-αlevels were elevated in patients clinically diagnosed with PKD,suggesting that an inflammatory response is involved in the pathogenesis of PKD.展开更多
An outbreak of a novel coronavirus was reported in Wuhan,China,in late 2019.It has spread rapidly through China and many other countries,causing a global pandemic.Since February 2020,over 28 countries/regions have rep...An outbreak of a novel coronavirus was reported in Wuhan,China,in late 2019.It has spread rapidly through China and many other countries,causing a global pandemic.Since February 2020,over 28 countries/regions have reported confirmed cases.Individuals with the infection known as coronavirus disease-19(COVID-19)have similar clinical features as severe acute respiratory syndrome first encountered 17 years ago,with fever,cough,and upper airway congestion,along with high production of proinflammatory cytokines(PICs),which form a cytokine storm.PICs induced by COVID-19 include interleukin(IL)-6,IL-17,and monocyte chemoattractant protein-1.The production of cytokines is regulated by activated nuclear factor-kB and involves downstream pathways such as Janus kinase/signal transducers and activators transcription.Protein expression is also regulated by post-translational modification of chromosomal markers.Lysine residues in the peptide tails stretching out from the core of histones bind the sequence upstream of the coding portion of genomic DNA.Covalent modification,particularly methylation,activates or represses gene transcription.PICs have been reported to be induced by histone modification and stimulate exudation of hyaluronic acid,which is implicated in the occurrence of COVID-19.These findings indicate the impact of the expression of PICs on the pathogenesis and therapeutic targeting of COVID-19.展开更多
Traumatic brain injury (TBI) results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration o...Traumatic brain injury (TBI) results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration of peripheral macrophages, which phagocytose debris and/or secrete a range of cytokines, chemokines and oth- er factors which modify the injured environment to promote or inhibit repair (Schwartz et al., 2013). The reactive macro- phages/microglia are broadly divided into two categories.展开更多
基金Supported by Agencies viz Department of Biotechnology(DBT),Indian Council of Medical Research(ICMR),Department of Science and Technology(DST)and Centre of Excellence(COE),UP Government,India for generous grants to our laboratory for diabetes research
文摘Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.
基金the Shenzhen City Science and Technology Bureau of China(No.JCYJ20170307111755218)“San-Ming”Project of Medicine in Shenzhen(No.SZSM201612092).
文摘Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.
文摘In our previous study,we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen,progesterone and estrogen receptor in rats with stimulated ovulation.However,the mechanism is not clear.This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism.The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin(PMSG)and human chorionic gonadotropin(HCG).Then the rats were randomly divided into model group(M),Shoutai pills group(S),progesterone group(P)and normal group(N).All the pregnant rats were treated from the first day.The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively,and N and M groups were given the same volume of normal saline and distilled water respectively.After treatment for 7 days,the animals were executed for serum and uterine tissues.The ELISA method was adopted to detect the contents of Thl cytokines[interferon-γ(INF-γ),interleukin-2(IL-2)]and Th2 cytokines(IL-4,IL-6,IL-10).The expression of leukemia inhibitory factor(L1F)and leukemia inhibitory factor receptor(LIFR)was detected by Western blotting and real-time PCR.As compared with N group,the expression levels of IFN-y and IL-2 in M group were significantly increased,and those of IL-4,IL-6,IL-10.LIF and LIFR were significantly decreased(P<0.05).As compared with M group,the levels of IL-4,IL-6,IL-10,LIF and LIFR in S group were significantly increased(P<0.05),and those of IFN-γand IL-2 were significantly decreased(P<0.05).It was suggested that Shoutai pills can increase the levels of IL-4.1L-6,IL-10,LIF and LIFR as well as reduce the levels of INF-γand IL-2 in rats with stimulated ovulation.The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balanee of Th1/Th2 cytokines.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning(NRF-2017R1A2B4005915)
文摘Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.
基金supported by three programs from the National Natural Science Foundation of China (NSFC) (The experimental study on the effect of trace elements iodine and selenium on the autoimmune thyroid disease (No.30571564)The cross-sectional investigation on hypothyroidism induced by excess iodine intake and the experimental research on pathogenesy (No.30972465)The change of thyroid pathology and the levels of T3,T4 in SePP1,GPX3 knock out mice (No.30810103004)
文摘Selenium (Se) is an essential trace element. Autoimmune thyroid diseases (AITD) are destructive inflammatory or anti-receptor autoimmune diseases characterized by reactivity to self-thyroid antigens. However, the effects of Se on the cytokines in AITD are still unclear. So we researched the role of Selenium (Se) and Thl/Th2 cytokine productions in the pathogenesis of autoimmune thyroid diseases (AITD).
文摘Coronavirus disease 2019(COVID-19)is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2(SARS-CoV-2)that is associated with a high spreading and mortality rate.On the date this review was written,SARS-CoV-2 infected about 96 million people and killed about 2 million people.Several arguments disclosed the high mortality of COVID-19 due to acute respiratory distress syndrome or change in the amount of angiotensin-converting enzyme 2(ACE2)receptor expression or cytokine storm strength production.In a similar pattern,hepatic impairment patients co-infected with SARS-CoV-2 exhibited overexpression of ACE2 receptors and cytokine storm overwhelming,which worsens the hepatic impairment and increases the mortality rate.In this review,the impact of SARS-CoV-2 on hepatic impairment conditions we overviewed.Besides,we focused on the recent studies that indicated cytokine storm as well as ACE2 as the main factors for high COVID-19 spreading and mortality while hinting at the potential therapeutic strategies.
基金Supported by National Natural Science Foundation of China,No.81872036Talent Innovation and Entrepreneurship Plan of Chengguan District of Lanzhou City,No.2019RCCX0038Science and Technology Plan of Chengguan District of Lanzhou City,No.2019JSXC0092.
文摘BACKGROUND Chronic hepatitis B virus infection remains a major global public health problem.Peginterferon-alpha-2a(PEG-IFN)has direct antiviral and immunoregulatory effects,and it has become one of the first choice drugs for the treatment of chronic hepatitis B(CHB).Cytokines play an important role in immunity,and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response.AIM To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB.METHODS Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients.RESULTS The monokine induced by INF-γ(CXCL9)and serum interferon-inducible protein 10(IP-10)levels at baseline were higher in virological responders than in nonvirological responders(NRs)and decreased during treatment,whereas the NRs did not exhibit significant changes.The macrophage inflammatory protein 1d(MIP-1d)levels at baseline and during treatment were significantly higher in the virological responders than in the NRs,while thymus and activation-regulated chemokine(TARC)levels at baseline and during treatment were significantly lower in the virological responders than in the NRs.The CXCL9,IP-10,MIP-1d,and TARC baseline levels exhibited the expected effects for interferon treatment.The area under the receiver operating characteristic curve values of CXCL9,IP-10,MIP-1d,and TARC for predicting virological responses were 0.787,0.799,0.787,and 0.77(P=0.01,0.013,0.01,and 0.021),respectively.CONCLUSION We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN.Therefore,cytokines can be used as an indicator of antiviral drug selection before CHB treatment.
基金supported by grants from the National Natural Science Foundation of China(No.81171495,No.81271765,and No.81400970)
文摘Liopxin A4(LXA4) is considered to be a crucial modulator in the inflammatory responses. In the present study, we aimed to study the effect of LXA4 on the inflammatory cytokines production induced by lipopolysaccharide(LPS) and the possible mechanism in normal human epidermal keratinocytes(NHEKs). NHEKs were isolated and cultured. The expression of toll-like receptor 4(TLR4), LXA4 receptor(ALXR) and aryl hydrocarbon receptor(Ah R) in NHEKs was detected by reverse transcription polymerase chain reaction(RT-PCR). The m RNA and protein levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1β(IL-1β) were determined in NHEKs stimulated by LPS(10 μg/m L) with or without preincubation with LXA4(100 nmol/L) for 30 min by real-time quantitative PCR(real-time q PCR) and enzyme-linked immunosorbent assay(ELISA), respectively. The expression levels of tumor necrosis factor receptor-associated factor 6(TRAF6) and suppressors of cytokine signaling 2(SOCS2) m RNAs and proteins, and nuclear translocation of NF-k B-p65 were measured by real-time q PCR and Western blotting, respectively. The results showed that NHEKs expressed TLR4, ALXR and Ah R. LXA4 significantly inhibited the m RNA and protein expression levels of TNF-α, IL-1β and TRAF6 induced by LPS in NHEKs, and LXA4 obviously increased the expression of SOCS2 at m RNA and protein levels. The nuclear NF-k B-p65 protein expression induced by LPS was inhibited after preincubation with LXA4 in NHEKs. It was concluded that LXA4 inhibits the LPS-induced production of TNF-α and IL-1β in NHEKs by up-regulating SOCS2 and down-regulating TRAF6.
基金grants from the science Research Foundation of Health Department of Hubei Province,China (No. JXIB048)the Janssen Research Foundation
文摘In order to investigate the expression of Th1 and Th2 cytokines in the vaginal candidiasis caused by Candida, the fungal vaginitis model was established in female ICR mice by intravaginal inoculation of suspension of C. albicans after the animals were pretreated with estradiol. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-2, IL-4, IL-10 and TGF-β1 in the vagina in the mice of different groups at different time points after the beginning of the experiment. The average expression level of IL-2 mRNA in group D (estrogen-treated mice) was significantly higher than that in groups H (estrogen-untreated mice) and I (control group) on the day 2. The average expression level of IL-4 mRNA in group D was significantly higher than that in groups I and H on the day 5. The average expression level of IL-10 mRNA in group D was significantly higher than that in groups H and I from day 7 to 11. The average expression level of TGF-β1 mRNA in group D was significantly higher than that in groups H and I at all time points. It was concludes that the high-level expression of IL-2 mRNA during early infection was associated with clearance of mucosal C. albicans, and the high-level expression of IL-10 mRNA during late stage of the infection was related to susceptibility to infection. TGF-β1 may play a predominant role when the virtual absence of changes in other Th-type cytokines during infection.
文摘目的探索初治慢性乙型肝炎(CHB)患者血清中细胞因子表达水平及其与病毒载量和肝脏炎症程度的关系,以期为临床动态评估CHB的病情和预后提供新思路。方法选择2018年10月至2019年11月就诊于海军军医大学(第二军医大学)第一附属医院感染科的初治慢性乙型肝炎病毒(HBV)感染者68例,健康对照者12名,通过ELISA检测血清中细胞因子IL-17A、IL-2、IL-21和IL-4表达水平,化学发光法检测HBV血清学标志物,qPCR法检测血清HBV DNA定量,全自动生化分析仪检测肝功能指标。采用Spearman相关分析评估血清细胞因子与病毒载量及肝脏炎症程度的相关性,绘制ROC曲线评价血清细胞因子水平对肝脏炎症程度的判断效能。结果相较于健康对照者,初治CHB患者血清IL-17A[17.50(11.99,25.36)pg/mL vs 13.74(9.07,16.94)pg/mL,Z=-2.001,P=0.045]、IL-21[37.12(23.85,77.66)pg/mL vs 20.30(17.90,24.19)pg/mL,Z=-3.485,P<0.01]水平升高,IL-2[57.19(31.10,79.92)pg/mL vs 73.06(62.41,105.84)pg/mL,Z=-2.509,P=0.012]水平降低,IL-4[11.40(5.79,18.62)pg/mL vs 10.84(8.05,25.20)pg/mL,Z=-0.681,P=0.496]水平差异无统计学意义。不同病程CHB患者的IL-17A表达水平差异有统计意义(H=8.870,P=0.031)。与非活动状态患者相比,炎症活动状态CHB患者血清中IL-17A[17.71(12.25,27.92)pg/mL vs 16.51(6.29,20.22)pg/mL]和IL-21[39.29(24.71,83.19)pg/mL vs 25.06(19.37,49.43)pg/mL]水平升高、IL-2[57.19(31.10,77.68)pg/mL vs 71.24(48.07,117.39)pg/mL]水平下降(均P<0.05),IL-4[11.40(5.94,18.12)pg/mL vs 14.57(3.12,24.49)pg/mL]水平差异无统计学意义(P>0.05)。HBeAg阳性CHB患者、HBeAg阴性CHB患者血清IL-17A[15.34(10.65,25.04)、19.98(15.55,34.14)pg/mL vs 13.74(9.07,16.94)pg/mL,H=10.061,P=0.007]和IL-21[37.74(25.06,82.87)、51.74(23.32,83.82)pg/mL vs 20.30(17.90,24.19)pg/mL,H=12.444,P=0.002]水平高于健康对照者,IL-2[57.19(37.45,79.92)、37.45(18.32,73.06)pg/mL vs 73.06(62.41,105.84)pg/mL,H=6.576,P=0.037]水平低于健康对照者。初治CHB患者血清IL-17A、IL-21、IL-4水平与HBV DNA定量无相关性(r=0.02、0.23、0.07,均P>0.05),IL-2水平与HBV DNA定量存在弱相关性(r=0.32,P=0.01)。初治CHB患者血清IL-17A、IL-21水平与丙氨酸转氨酶(ALT)水平(r=0.59、0.49,均P<0.01)和天冬氨酸转氨酶(AST)水平(r=0.47、0.36,均P<0.01)均存在相关性,而IL-2、IL-4水平与ALT、AST水平均无相关性(均P>0.05)。ALT≥300 U/L初治CHB组、ALT<300 U/L初治CHB组及健康对照组间血清IL-17A、IL-2、IL-21水平差异有统计学意义(均P<0.05),其中ALT≥300 U/L初治CHB组IL-17A、IL-21水平均高于ALT<300 U/L初治CHB组及健康对照组(均P<0.01),ALT<300 U/L初治CHB组IL-2水平低于健康对照组、IL-21水平高于健康对照组(均P<0.01)。ROC曲线分析结果显示,IL-17A判断肝脏炎症程度的AUC值为0.8933(95%CI 0.7930~0.9936),IL-21判断肝脏炎症程度的AUC值为0.7600(95%CI 0.6227~0.8973)。结论IL-17A、IL-2和IL-21参与慢性HBV感染进程。初治CHB患者无论HBeAg阳性与否或炎症程度高低,血清IL-17A和IL-21水平均升高,IL-2水平均下降;IL-2与HBV DNA定量有一定相关性;IL-17A和IL-21与ALT及AST均存在正相关;检测IL-17A和IL-2有助于病情评估与预后判断。
文摘Objective:To assess the association between genetic variants of transferrin receptor 2(TFR2)exon 4 and anemia status and to describe the expression levels of several cytokines,hepcidin,soluble transferrin receptor and erythropoietin.Methods:Institutional based comparative study was done randomly to recruit 106 pregnant women who attended antenatal care in three different health centers in Boyolali Regency,Central Java from May 2015 to September 2015.DNA was extracted from peripheral blood samples of selected pregnant women and sequencing was done for TFR2 exon 4.Furthermore,enzyme-linked immunosorbent assay was conducted to measure the expression levels of interleukin 6,interleukin 4,transforming growth factorβand iron-metabolism related proteins such as hepcidin,soluble transferrin receptor,and erythropoietin.Gene alignment was performed by using a CLUSTAL W program.Collected data were analyzed statistically by using parametric and nonparametric tests with Statistical Product and Service Solutions(SPSS)20.0 for Windows.Results:Three novel genetic variants from TFR2 exon 4(position 603,605 and 606)were associated with anemia status.Moreover,the expression levels of interleukin 6,interleukin 4,transforming growth factorβand erythropoietin were higher in anemic pregnant women than those of nonanemic pregnant women but only erythropoietin level reached statistical significance.These results were followed by decreases of hepcidin and soluble transferrin receptor levels.Conclusions:Various factors contribute to anemia prevalence among pregnant women in Boyoali Regency,Central Java,Indonesia.Our novel findings showed that TFR2 exon 4 has 3 mutational sites in position 603,605 and 606.These novel genetic variants may provide a new insight into the role of TFR2 in anemia.
基金supported by the National Natural Science Foundation of China(U1703118)Natural Science Foundation of Jiangsu Province(No.BK20181364)+6 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.19KJA310003)Scientific Research Foundation of Jiangsu health and Health Committee(No.H2018087)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Jiangsu Shuangchuang ProgramOpen Funds of the State Key Laboratory for Chemo/Biosensing and Chemometrics(2016015)Open project of the National Laboratory of Biomacromolecules(2017kf05)the cooperative project between Southeast University and Nanjing Medical University(2018DN0004)Jiangsu Specially-Appointed Professor project,China。
文摘With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations,it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels.In this study,we quantitatively determined the expression levels of T-helper 2(Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR.The recorded kinetic profiles resulting from the immunization of ovalbumin(OVA) indicated that after immunization,Th2 cytokines including interleukin(IL) families such as IL-4,IL-10,and IL-13 in the camels were up-regulated by a factor of 1.78,3.15,and 1.22,respectively,which was validated by traditional enzyme-linked immunosorbent assay(ELISA) methods.Unlike ELISA which requires specific enzyme-labeled antibodies,this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision,which is meaningful for biomedical explorations of camel-derived antibodies.
基金This work was supported by the Natural Science Foundation of Hubei Province(No.2019CFB753)the Hubei Technological Innovation Special Fund(No.2019ACA132)the Hubei Natural Science Foundation(No.2020CFB805).
文摘Objective Paroxysmal kinesigenic dyskinesia(PKD)is a rare movement disorder PRRT2 gene mutations have been reported to cause PKD.However,the pathophysiological mechanism of PKD remains unclear,and it is unknown whether an inflammatory response is involved in the occurrence of this disease.We aimed to investigate the symptomatology,genotype,and serum cytokines of patients with PKD.Methods We recruited 21 patients with PKD,including 7 with familial PKD and 14 with sporadic PKD.Their clinical features were investigated,and blood samples were collected,and PRRT2 mutations and cytokine levels were detected.Results The mean age at PKD onset was 12.3±2.2 years old.Dystonia was the most common manifestation of dyskinesia,and the limbs were the most commonly affected parts.All attacks were induced by identifiable kinesigenic triggers,and the attack durations were brief(<1 min).Four different mutations from 9 probands were identified in 7 familial cases(71.4%)and 14 sporadic cases(28.6%).Two of these mutations(c.649dupC,c.620_621delAA)had already been reported,while other 2(c.1018_1019delAA,c.1012+1G>A)were previously undocumented.The tumor necrosis factor(TNF)-αlevel in the PKD group was significantly higher than that in the age-and sex-matched control group(P=0.025).There were no significant differences in the interleukin(IL)-1β,IL-2R,IL-6,IL-8,or IL-10 levels between the two groups.Conclusion In this study,we summarized the clinical and genetic characteristics of PKD.We found that the serum TNF-αlevels were elevated in patients clinically diagnosed with PKD,suggesting that an inflammatory response is involved in the pathogenesis of PKD.
基金Medical Scientific Research Foundation of Guangdong Province of China,Guangdong Provincial Health Commission,China,No.A2018356。
文摘An outbreak of a novel coronavirus was reported in Wuhan,China,in late 2019.It has spread rapidly through China and many other countries,causing a global pandemic.Since February 2020,over 28 countries/regions have reported confirmed cases.Individuals with the infection known as coronavirus disease-19(COVID-19)have similar clinical features as severe acute respiratory syndrome first encountered 17 years ago,with fever,cough,and upper airway congestion,along with high production of proinflammatory cytokines(PICs),which form a cytokine storm.PICs induced by COVID-19 include interleukin(IL)-6,IL-17,and monocyte chemoattractant protein-1.The production of cytokines is regulated by activated nuclear factor-kB and involves downstream pathways such as Janus kinase/signal transducers and activators transcription.Protein expression is also regulated by post-translational modification of chromosomal markers.Lysine residues in the peptide tails stretching out from the core of histones bind the sequence upstream of the coding portion of genomic DNA.Covalent modification,particularly methylation,activates or represses gene transcription.PICs have been reported to be induced by histone modification and stimulate exudation of hyaluronic acid,which is implicated in the occurrence of COVID-19.These findings indicate the impact of the expression of PICs on the pathogenesis and therapeutic targeting of COVID-19.
基金supported by the National Health and Medical Research Council of AustraliaProject grant 1045125 and Fellowship(to AMT)628344support from Stem Cells Australia
文摘Traumatic brain injury (TBI) results in a range of neuroinflam- matory events that vary depending on the type and extent of in- jury. Central to this is the activation of tissue resident microglia and infiltration of peripheral macrophages, which phagocytose debris and/or secrete a range of cytokines, chemokines and oth- er factors which modify the injured environment to promote or inhibit repair (Schwartz et al., 2013). The reactive macro- phages/microglia are broadly divided into two categories.