Th17和调节性T细胞在人类免疫缺陷病毒疾病进展中的作用及其调控机制

目的本研究通过观察人类免疫缺陷病毒(HIV)感染者外周血Th17、Treg细胞及其相关转录因子、细胞因子的表达,进一步揭示Th17、Treg细胞的调控机制及其在HIV感染者疾病进展中的作用。方法选取2019年1月—2019年10月河南省上蔡县HIV感染者80例作为研究组,选取同地区健康人群20例作为对照组。采用流式细胞术检测外周血CD4^(+)T、CD8^(+)T及外周血单个核细胞Th17、Treg,酶联免疫吸附试验检测血浆中细胞因子白细胞介素-17(IL-17)、IL-23水平,实时聚合酶链反应检测转录因子ROR-γt及Foxp3 mRNA表达,Pearson法分析Th17、Treg与CD4^(+)T的相关性。结果研究组CD4^(+)T、CD4^(+)T/CD3+T、CD4^(+)T/CD8^(+)T低于对照组(P<0.05),CD8^(+)T和CD8^(+)T/CD3+T高于对照组(P<0.05)。研究组Th17/CD4^(+)T、Th17/Treg低于对照组(P<0.05),Treg/CD4^(+)T高于对照组(P<0.05)。研究组ROR-γtmRNA高于对照组(P<0.05),Foxp3mRNA低于对照组(P<0.05)。研究组IL-17、IL-23水平低于对照组(P<0.05)。Pearson相关性分析结果表示,Th17细胞百分比与CD4^(+)T细胞计数呈正相关(r=0.293,P<0.05),Treg细胞百分比与CD4^(+)T细胞计数呈负相关(r=-0.198,P<0.05)。结论HIV感染能降低Th17细胞、升高Treg细胞,破坏机体免疫平衡,其机制与调控转录因子ROR-γt、Foxp3及细胞因子IL-17、IL-23表达有关,Th17细胞、Treg细胞与HIV感染者疾病进展密切相关。

Neutrophil-derived interleukin-17A participates in neuroinflammation induced by traumatic brain injury

After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.

Drug-induced entero-colitis due to interleukin-17 inhibitor use;capsule endoscopic findings and pathological characteristics:A case report

BACKGROUND Interleukin-17(IL-17)inhibitors are known to cause exacerbation or new onset of inflammatory bowel disease upon administration.However,few reports have described characteristic endoscopic and histopathologic findings,and no small intestinal lesions have been reported so far.CASE SUMMARY A woman in her 60s with psoriasis was administered ixekizumab(IXE),an anti-IL-17A antibody,for the treatment of psoriasis.Twenty months after commencing treatment,the patient visited our hospital because of persistent diarrhea.Blood tests performed at the time of the visit revealed severe inflammation,and colonoscopy revealed multiple round ulcers throughout the colon.A tissue biopsy of the ulcer revealed infiltration of inflammatory cells and granuloma-like findings in the submucosal layer.Capsule endoscopy revealed multiple jejunal erosions.After the withdrawal of IXE,the symptoms gradually improved,and ulcer reduction and scarring of the colon were endoscopically confirmed.CONCLUSION To the best of our knowledge,17 reports have documented IL-17 inhibitorinduced entero-colitis with endoscopic images,endoscopic findings,and pathological characteristics,including the present case.Nine of these cases showed diffuse loss of vascular pattern,coarse mucosa/ulcer formation in the left colon,and endoscopic findings similar to those of ulcerative colitis.In the remaining eight cases,discontinuous erosions and ulcerations from the terminal ileum to the rectum were seen,with endoscopic findings similar to those of Crohn’s disease.In this case,the findings were confirmed by capsule endoscopy,which has not been previously reported.

Flavonoids in safflower extract reduce cisplatin-induced damage to human follicle dermal papilla cells by inhibiting DNA damage and Rad17/Chk1/Cdc25C signaling

Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.

Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

17-DMAG对PD-1人源化小鼠肝癌移植瘤的抑制作用

目的 探讨17-二甲基胺乙基-17-去甲氧基格尔德霉素(17-DMAG)对PD-1人源化小鼠人肝癌移植肿瘤生长的抑制作用。方法 选取30只PD-1人源化小鼠,将HepG2细胞悬液注射于小鼠右侧腹股沟皮下组织,构建人肝癌移植瘤模型;将荷瘤人源化小鼠随机分为3组(每组10只):(1)模型组(注射生理盐水10 mg/kg);(2)17-DMAG组(按25 mg/kg腹腔注射17-DMAG,3次/周);(3)顺铂组(腹腔注射20 mg/kg, 2次/周),实验持续4周。注射结束后测量人源化小鼠移植瘤的长、短径计算体积,测量肿瘤质量计算抑瘤率,同时采用免疫组化方法检测肿瘤组织中CD31(以阳性细胞数计算肿瘤微血管密度(MVD))及血管内皮生长因子(VEGF)的表达。结果 17-DMAG组和顺铂组的肿瘤体积和质量均较模型组显著减小(P<0.05),17-DMAG组的抑瘤率略高于顺铂组,但17-DMAG组和顺铂组肿瘤质量和体积以及抑瘤率均不存在显著性差异。17-DMAG组和顺铂组MVD标记微血管数量及VEGF表达均低于模型组(P<0.05),且17-DMAG组又低于顺铂组(P<0.05)。结论 17-DMAG可显著降低肝癌移植瘤中VEGF的表达,抑制新生血管在肿瘤中发生发展,从而对人源化小鼠肝癌移植瘤发挥抑制作用。

HPV DNA负荷量、辅助性T细胞17、FoxP3+调节性T细胞及炎症因子与高危型HPV感染的相关性分析

目的探讨人乳头瘤病毒(HPV)DNA、辅助性T细胞17(Th17)、叉头状转录因子3阳性(FoxP3^(+))调节性T细胞(Treg)及宫颈灌洗液中炎症因子与高危型HPV感染的相关性,为高危型HPV感染防治提供新思路。方法将2020年9月至2021年2月该院收治的高危型HPV感染患者100例纳入研究作为研究组,然后将其中50例高危型HPV16/18阳性患者作为HPV16/18组,50例其他12种高危型阳性病例作为其他亚型组。另外,选取同期体检的健康女性作为对照组(n=50)。比较研究组和对照组HPV DNA负荷量、Th17、FoxP3^(+)Treg及宫颈灌洗液中炎症因子[白细胞介素(IL)-10、肿瘤坏死因子α(TNF-α)、IL-17A]水平,比较HPV16/18组和其他亚型组各项指标水平,比较不同宫颈病变患者各项指标水平。分析各项指标与高危型HPV感染、宫颈病变的相关性,以及对宫颈病变患者高危型HPV感染的诊断价值。结果研究组HPV DNA负荷量、Th17、FoxP3^(+)Treg及宫颈灌洗液中IL-10、TNF-α、IL-17A水平均高于对照组(P<0.05),HPV16/18组各项指标水平均高于其他亚型组(P<0.05)。不同宫颈病变患者各项指标水平比较,差异有统计学意义(P<0.05)。HPV DNA负荷量、FoxP3^(+)Treg、Th17及宫颈灌洗液中IL-10、TNF-α、IL-17A水平与高危型HPV感染分型(HPV16/18=1,其他亚型=2)均呈负相关(P<0.05),与宫颈病变(宫颈上皮内瘤变Ⅰ级=1,宫颈上皮内瘤变Ⅱ级=2,宫颈上皮内瘤变Ⅲ级=3,宫颈癌=4)均呈正相关(P<0.05)。各项指标联合诊断高危型HPV16/18阳性的曲线下面积(AUC)为0.911(95%CI:0.837~0.959),大于各指标单独诊断。结论高危型HPV感染患者HPV DNA负荷量、Th17、FoxP3^(+)Treg及炎症因子水平异常,与高危型HPV感染分型、宫颈病变密切相关,而且HPV DNA负荷量与Th17、FoxP3^(+)Treg、炎症因子相关,各项指标联合检测可为临床防治高危型HPV持续感染提供可靠依据。

宫颈鳞状上皮内病变和宫颈癌Th17、HIF-1α水平变化与HPV感染的关系

目的探讨宫颈鳞状上皮内病变(SIL)和宫颈鳞状细胞癌(SCC)辅助性T细胞17(Th17)、缺氧诱导因子-1α(HIF-1α)水平变化与人乳头瘤病毒(HPV)感染的关系。方法收集2020年1月至2023年1月于金寨县人民医院病理科就诊的40例宫颈SIL患者(SIL组)、40例宫颈SCC患者(SCC组)的病理组织和静脉血指标,并收集同期同一医院20例行全子宫切除的患者(对照组)的正常宫颈上皮组织和静脉血指标。对三组Th17、HIF-1α水平及HPV阳性感染率进行检测并比较。结果SCC组和SIL组Th17、HIF-1α水平显著高于对照组(P<0.05),且SCC组高于SIL组(P<0.05)。SCC组和SIL组HPV单一、多重感染率比较无统计学差异(P>0.05);HPV感染患者的Th17、HIF-1α水平均显著高于未感染患者(P<0.05),且多重感染患者的Th17和HIF-1α水平显著高于单一感染患者(P<0.05)。Th17、HIF-1α水平与HPV感染呈显著相关(P<0.05),且两种指标之间亦存在显著相关(P<0.05)。结论Th17、HIF-1α水平可作为SCC患者预后的客观预测指标及指导临床治疗的参考。

血清可溶性人类白细胞抗原G、白介素-17水平预测先兆流产患者保胎结局的研究

目的 分析血清可溶性人类白细胞抗原G(sHLA-G)、白介素-17(IL-17)水平预测先兆流产患者保胎结局的价值。方法 选取2018年1月至2020年6月在海南省中医院接受保胎治疗的90例先兆流产患者作为研究对象,于治疗10d时根据保胎结局分为成功组(n=71)与失败组(n=19)。统计患者相关资料,分析治疗前血清sHLA-G、IL-17水平预测先兆流产患者保胎结局的价值。结果 90例患者中保胎失败19例,占21.11%;失败组与成功组血清sHLA-G、IL-17、孕酮(P)水平比较,差异具有统计学意义(P<0.05);受试者工作特征(ROC)曲线显示,先兆流产患者保胎治疗前血清sHLA-G、IL-17水平预测保胎失败风险的曲线下面积(AUC)均>0.80,均有较理想的预测价值,且联合预测价值最高。结论 保胎治疗前血清sHLA-G低表达、IL-17过表达可能提示先兆流产患者保胎失败风险高。

Interleukin-17 plays a critical role in the acute rejection of intestinal transplantation

AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A metaanalysis

AIM:To investigate the associations of interleukin-17(IL-17)genetic polymorphisms and serum levels with ulcerative colitis(UC)risk.METHODS:Relevant articles were identified through a search of the following electronic databases,excluding language restriction:(1)the Cochrane Library Database(Issue 12,2013);(2)Web of Science(1945-2013);(3)PubMed(1966-2013);(4)CINAHL(1982-2013);(5)EMBASE(1980-2013);and(6)the Chinese Biomedical Database(1982-2013).Meta-analysis was conducted using STATA 12.0 software.Crude odds ratios and standardized mean differences(SMDs)with corresponding95%confidence intervals(CIs)were calculated.All of the included studies met all of the following five criteria:(1)the study design must be a clinical cohort or a case-control study;(2)the study must relate to the relationship between IL-17A/F genetic polymorphismsor serum IL-17 levels and the risk of UC;(3)all patients must meet the diagnostic criteria for UC;(4)the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels;and(5)the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium(HWE).The Newcastle-Ottawa Scale(NOS)criteria were used to assess the methodological quality of the studies.The NOS criteria included three aspects:(1)subject selection:0-4;(2)comparability of subjects:0-2;and(3)clinical outcome:0-3.NOS scores ranged from 0 to 9,with a score≥7 indicating good quality.RESULTS:Of the initial 177 articles,only 16 case-control studies met all of the inclusion criteria.A total of1614 UC patients and 2863 healthy controls were included in this study.Fourteen studies were performed on Asian populations,and two studies on Caucasian populations.Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models(P<0.001 for all).The results also showed that UC patients had higher serum IL-17 levels than healthy controls(SMD=5.95,95%CI:4.25-7.65,P<0.001).Furthermore,serum IL-17 levels significantly correlated with the severity of UC(moderate vs mild:SMD=2.59,95%CI:0.03-5.16,P<0.05;severe vs mild:SMD=7.09,95%CI:3.96-10.23,P<0.001;severe vs moderate:SMD=5.84,95%CI:5.09-6.59,P<0.001).The NOS score was≥5 for all of the included studies.Based on the sensitivity analysis,no single study influenced the overall pooled estimates.Neither the Begger’s funnel plots nor Egger’s test displayed strong statistical evidence for publication bias(IL-17A/F genetic polymorphisms:t=-2.60,P=0.019;serum IL-17 levels:t=-1.54,P=0.141).CONCLUSION:The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC.

Polymorphism in the interleukin-17A promoter contributes to gastric cancer

AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer

BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.

Expression of Interleukin-17 in Lung and Peripheral Blood of Asthmatic Rats and the Influence of Dexamethasone

The expression of interleukin-17 （IL-17） in lung and peripheral blood of asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the pathogenesis of asthma were investigated. Thirty Sprague-Dawley （SD） adult rats were randomly divided into three groups （n=10 in each group）： normal group, asthmatic group, and dexamethasone-interfered group. Rat asthmatic model was established by intraperitoneal （i.p.） injection of 10% ovalbumin （OVA） and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone （2 mg/kg, i.p.） 30 min before each challenge. The expression of IL-17 protein in serum and bronchoalveolar lavage fluid （BALF） was detected by ELISA. The expression of IL-17 mRNA in peripheral blood mononuclear cells （PBMC） and BALF cells was semi-quantitatively detected by RT-PCR. The expression of IL-17 protein in serum and BALF of asthmatic rats was significantly elevated as compared with normal rats and dexamethsone-interfered rats （P〈0.01）, and there was significant difference between normal rats and dexamethsone-interfered rats （P〈0.05）. The expression of IL-17 mRNA in PBMC and BALF cells of asthmatic rats was markedly increased as compared with normal rats and dexamethsone-interfered rats （P〈0.01）, and significant difference was found between normal rats and dexamethsone-interfered rats （P〈0.05）. It was concluded that the expression of IL-17 was increased significantly in asthmatic rats and could be inhibited partly by dexamethasone, suggesting that IL-17 might play an important role in the pathogenesis of asthma as an inflammation regulation factor.

The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL-17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1.1416±0.0591, which was significantly higher than that in normal controls (0.8788±0.0344, P<0.001). The expression levels of IFN-γ mRNA were 1.1142±0.0561 and 0.9050±0.0263, respectively, with significant difference(P<0.001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1.1397±0.0521, which was markedly higher than that in normal controls (0.8681±0.0308, P<0.001). These findings indicate that up-regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients

AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.

Unexpected alliance between syndecan-1 and innatelike T cells to protect host from autoimmune effects of interleukin-17

Innate-like T cells, namely natural killer T(NKT) and γδ T cells, play critical roles in linking innate and adaptive immune responses through rapid production of cytokines. Prominent among these cytokines is interleukin-17(IL-17), which is a potent proinflammatory cytokine that plays a critical role in host defense against fungi and extracellular bacteria. However, excessive IL-17-production promotes autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. IL-17 has also been implicated in regulating body fat, which is highly relevant given rises in obesity and type 2 diabetes. NKT cells, γδ T cells and mucosal-associated invariant T cells(MAIT) are the major sources of IL-17 involved in protection of mucosal surfaces from opportunistic infections and causing autoimmunity when become dysregulated. Given the pathogenic effects of IL-17, efforts have been directed towards understanding mechanisms that guard against IL-17 overproduction. One novel potent mechanism is mediated by the heparan sulfate proteoglycan, syndecan-1(sdc1), which is selectively expressed by IL-17-producing subsets of NKT and γδ T cells. This unexpected role for sdc1 is uncovered by analysis of NKT and γδ T cells in sdc1-deficient mice. In this mini-review, we discuss selective expression of sdc1 by these innate T cells and consequences of its absence on IL-17 homeostasis and pathological implications.

Suppressive effect of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on inflammation by regulation of NF-κB pathway and interleukin-17 in mice with dextran sulphatesodium-induced ulcerative colitis

Objective:To investigate the effects of pectic polysaccharides extracted from Rauwolfia verticillata(Lour.) Baill.var.hainanensis Tsiang on an experimental murine colitis model.Methods:Experimental colitis was induced by dextran sulfate sodium(DSS),and mice were divided into 4 groups:control.DSS alone.DSS plus SASP,DSS plus pectic polysaccharides.The disease activity index(DAI) and histological score were observed.The tumor necrosis factor(TNF)-α and interleukin(IL)-17 levels were measured by enzyme-linked immunosorbent assay.I κ B and NF-κB p65 expression were assessed by western blot analysis.Myeloperoxidase(MPO) activity was determined by using MPO assay kit.Re.sults:Administration of pectic polysaccharides significantly reduced the severity of DSS-induced colitis as assessed by DAT and histological score,and resulted in down regulation of MPO activity and NF-κB p65 expression and subsequent degradation of IκB protein,strikingly reduced the production of TNF-α and IL-17.Conclusions:Pectic polysaccharides extracted from Rauvolfia verticillata(Lour.)Baill.var.hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.

Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation

Bone regeneration is a tightly regulated process that ensures proper repair and functionality after injury.The delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory response.Interleukin(IL)-17A,produced in the early phase of inflammation,influences the fate of osteoprogenitors.Due to their inherent capacity to differentiate into osteoblasts,mesenchymal stem/stromal cells(MSCs)contribute to bone healing and regeneration.This review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of MSCs.The main findings demonstrating IL-17A’s influence on osteoblastogenesis are described.To this end,divergent information exists about the capacity of IL-17A to regulate MSCs’osteogenic fate,depending on the tissue context and target cell type,along with contradictory findings in the same cell types.Therefore,we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17,which may help in the understanding of IL-17A function in bone repair and regeneration.

Interleukin-17A gene variants and risk of coronary artery disease:a large angiography-based study

Background Recent studies have also revealed that interleukin(IL)-17A plays a key role in atherosclerosis and its complication,but the relationship of its common variants with coronary artery disease(CAD) has not been extensively studied.Methods We systematically screened sequence variations in the IL17A gene and designed an angiog-raphy -based case-controlled study consisting of 1031 CAD patients and 935 control subjects to investigate the association between the selected polymorphisms of IL-17A gene and CAD risk in Chinese Han population.Results Frequencies of IL17A rs8193037 GG homozygote and G allele were significantly higher in the patient group than those in the control group(P【0.001;OR=0.68;95%CI=0.54-0.85).Stratification analysis showed that the IL17A rs8193037 G allele significantly increased the risk of CAD only among male subjects (P=0.001;OR=0.63;95%CI=0.47-0.83).After adjustment for conventional risk factors,binary logistic regression analysis showed that the G allele carriers(GG +AG) had significantly increased CAD risk compared with the AA homozygotes (adjusted P【0.001;OR 0.43;95%CI,0.33- 0.58).ELISA showed augmented IL17A production in plasma of the AMI patients.Conclusions Based on our data,we speculated that the SNP rs8193037 of IL17A gene is significantly associated with CAD risk in Chinese Han population and the rs8193037 G allele which is associated with increased expression of IL17A in AMI patients may be an independent predictive factor for CAD.