Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

Changes in soluble interleukin-2 receptor level in serum and Na^+ -K^+ -exchanging ATPase activity in semen of infertile men caused by antisperm antibody

Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.

Fluence of Glucosidorum Tripterygii Totorum on joint and serum soluble interleukin-2 receptor in patients with ankylosing spondylitis

Objective The current study was designed to find out the effect of Glucosidorum Tripterygii Totorum (GTT) on the serum level of soluble interleukin-2 receptor (sIL-2R) in patient with ankylosing spondylitis (AS). Method 29 patients with active AS were selected to take GTT (1mg per kg) three times a day for one year. After that, its curative effect was evaluated. The serum level of sIL-2R of these patients was measured by sandwich ELISA method and was compared with that of normal subjects. Result The serum level of sIL-2R in active AS patients was obviously higher than that of the non-active AS patients. (P<0.01). The total effective rate of GTT on AS was 89.6%, while clinical relief rate 27.6%, obvious effective rate 44.8%, effective rate 17.2% and non-effective rate 10.4%. The patients’ serum level of sIL-2R after therapy was significantly lower than that before therapy except patients with no effect. (P<0.05). Conclusion GTT has positive curative effect on active AS patients and could cause obvious decrease of the serum level of sIL-2R. The serum level of sIL-2R can be used as an important index of activity of AS and as a guide of therapy.

Study of the Effect of Leeching on Plasma Endothelin and Soluble Interleukin-2 Receptor in Patients with Systemic Lupus Erythematosus

Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes

Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.

Effects of Aprotinin on Serum Interleukin-2 and Soluble Interleukin-2 Receptor during Cardiopulmonary Bypass

Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.

Expression of estrogen receptor alpha,nerve growth factor,interleukin-2,and androgen receptor in the cerebellum of ovariectomized rats following soybean isoflavone treatment

BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.

INTERLEUKIN-2 (IL-2) PRODUCTION AND INTERLEUKIN-2 RECEPTOR EXPRESSION IN PATIENTS WITH APLASTIC ANEMIA

IL-2 production and IL-2 receptor (Tac antigen) of the peripheral blood mononuclear cells in 30 patients with aplastic anemic (AA) were studied. We found that mononuclear cells from patients produce spontaneously IL-2 in the absence of exogenous lee-tin stimulation, the proportion of Tac+ cells in mononuclear cells increased. The release of IL-2 and or Tac antigen expression were elevated in almost every patient with AA. The plasma from patients stimulate mitogen-induced blastogenesis and Tac antigen expression of normal human lymphocytes. Immunological 1 abnormalities of patients with AA possibly might represents secondary response to bone marrow depression.

CHANGES ON RECEPTOR EXPRESSIONAND PRODUCTION OF INTERLEUKIN-2 IN CIRCULATING LYMPHOCYTE POPULATION AFTER OPEN HEART SURGERY

To evaluate the change of perioperative cell mediated immunity after cardiac operation with cardiopul-monary bypass (CPB), so as to provide some information for timely prevention and treatment against post-operative immunological disorder, 40 patients were studied. By searching for the effects of CPB and anes-thesia, interleukln-2 receptor (IL-2R) expression upon the surface of peripheral blood mononuclear cells(PBMC), as well as interleukin-2 (IL-2) production in vitro was traced 55 min after anesthesia, at end ofCPB, on postoperative 1, 7, and 14 day versus preanesthesia control. Our data demonstrated that expres-sion of IL-2R on PBMC was significantly suppressed in all comparing with the baseline value, meanwhile,IL-2 production in vitro also statistically dropped. However,no statistical difference was found on perioper-ative IL 2R expression and IL-2 synthesis in the cholecystectomy group. We conclude that postoperativeimmunological disorder seems to be the main factor, which could be denoted as reduced IL 2R expressionon PBMC and lL-2 synthesis in vitro for sepsis, even multiple system organ failure developed after cardiacsurgery.

Role of P2X_7 receptors in the development of diabetic retinopathy

The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade

Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Argon preconditioning protects neuronal cells with a Toll-like receptor-mediated effect

The noble gas argon has the potential to protect neuronal cells from cell death.So far,this effect has been studied in treatment after acute damage.Preconditioning using argon has not yet been investigated.In this study,human neuroblastoma SH-SY5Y cells were treated with different concentrations of argon(25%,50%,and 74%;21%O_(2),5%CO_(2),balance nitrogen)at different time intervals before inflicting damage with rotenone(20μM,4 hours).Apoptosis was determined by flow cytometry after annexin V and propidium iodide staining.Surface expressions of Toll-like receptors 2 and 4 were also examined.Cells were also processed for analysis by western blot and qPCR to determine the expression of apoptotic and inflammatory proteins,such as extracellular-signal regulated kinase(ERK1/2),nuclear transcription factor-κB(NF-κB),protein kinase B(Akt),caspase-3,Bax,Bcl-2,interleukin-8,and heat shock proteins.Immunohistochemical staining was performed for TLR2 and 4 and interleukin-8.Cells were also pretreated with OxPAPC,an antagonist of TLR2 and 4 to elucidate the molecular mechanism.Results showed that argon preconditioning before rotenone application caused a dose-dependent but not a time-dependent reduction in the number of apoptotic cells.Preconditioning with 74%argon for 2 hours was used for further experiments showing the most promising results.Argon decreased the surface expression of TLR2 and 4,whereas OxPAPC treatment partially abolished the protective effect of argon.Argon increased phosphorylation of ERK1/2 but decreased NF-κB and Akt.Preconditioning inhibited mitochondrial apoptosis and the heat shock response.Argon also suppressed the expression of the pro-inflammatory cytokine interleukin-8.Immunohistochemistry confirmed the alteration of TLRs and interleukin-8.OxPAPC reversed the argon effect on ERK1/2,Bax,Bcl-2,caspase-3,and interleukin-8 expression,but not on NF-κB and the heat shock proteins.Taken together,argon preconditioning protects against apoptosis of neuronal cells and mediates its action via Toll-like receptors.Argon may represent a promising therapeutic alternative in various clinical settings,such as the treatment of stroke.

STUDY OF T－LYMPHOCYTE SUBSETS AND INTERLEUKIN－2 AND INTERLEUKIN－2 RECEPTOR OF RESPIRATORY SYNCYTIAL VIRUS PNEUMONIA

T-Lymphocyte subsets and humoral immune and the activity of IL-2 and IL-2R in respiratory syncytial virus (RSV) pneumonia in 26 cases were tested. The result showed in the patients with RSV pneumonia the averages of T3 and T4 were 37.56±1.46% and 27. 15±8. 02% respectively,They were significantly lower than 53.4 ±9.2% and 35.5±7.7% of averages of T3 and T4 in healthy controlled group (both. P< 0. 001 ), the average of T3 was 22. 73±7.06%, it was lower an 26. 7±6. 3 % of T8 in controlled group (P<0. 02 );the ratio of T4/T8 was 1. 245±0. 399 ,there was no significant difference from 1. 35 ±0. 17 of the ratio in controlled group (P > 0. 1). The mean value of IgG was 1. 177± 0. 3685g/L, it was significantly lower than 1. 427± 0. 498g/L of that in controlled group(P < 0. 005). The mean values of IgA and IgM were 0. 1136±0.0393g/L and 0. 768±0. 353g/L respectively, they were significantly lower than 0. 2706 ±0. 876g/L and 0. 122±0. 061g/L of IgA and IgM in controlled group. The activity of IL-2 and IL-2R were 17. 46 ±5. 79%, and 28. 32 ±5. 924% respectively, they were significantly lower than 30. 22 ±14. 55% and 39. 53±8. 61 % of those in healthy group (both P < 0. 001). The severe the pneuumonia, the greater the lowering of IL-2 and IL-2R. These about results suggested that RSV could greatly suppress the immune function of the patients, inducing secondary immunodeficiency, leading to repeated breather and asthma.

Soluble Interleukin 2 Receptor-Alpha (sIL-2Rα) in the Peripheral Blood of Dogs—Comparison of Malignant Neoplasia with Other Diseases

Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

黄芪注射液对银屑病外周血淋巴细胞白介素-2及其受体的影响

目的探讨黄芪注射液治疗银屑病的机制。方法应用流式细胞仪和酶联免疫吸附试验(ELISA)测定不同浓度黄芪注射液干预下银屑病患者外周血淋巴细胞上白介素-2膜受体(mIL-2R)的表达及培养上清液中白介素-2(IL-2)、可溶性白介素-2受体(sIL-2R)的变化。结果患者IL-2、sIL-2R升高,mIL-2R降低,与正常对照差异有显著性。低浓度黄芪促进IL-2、mIL-2R的表达,高浓度黄芪抑制IL-2表达,使mIL-2R的表达趋于正常。不同浓度黄芪注射液均抑制sIL-2R的表达,且随浓度增高抑制增强。结论黄芪注射液可调节银屑病外周血淋巴细胞IL-2及其受体的表达并存在剂量依赖关系。

TSH抑制疗法对分化型甲状腺癌患者术后血清Tg、VEGF、TSGF、CD44V6、sIL-2R及T淋巴细胞亚群水平的影响

目的:探讨促甲状腺激素(thyroid stimulating hormone,TSH)抑制疗法对分化型甲状腺癌(differentiated thyroid carcinoma,DTC)患者术后血清甲状腺球蛋白(thyroglobulin,Tg)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、肿瘤特异性生长因子(tumors pecific growth factor,TSGF)、白细胞分化抗原44变异型6(CD44V6)、可溶性白细胞介素-2受体(soluble interleukin-2receptor,sIL-2R)及T淋巴细胞亚群水平的影响。方法:选择2014年1月~2017年1月我院收治的接受甲状腺全切手术治疗的100例DTC患者,随机分为对照组和实验组,各50例。对照组患者常规给予甲状腺素替代治疗,实验组患者给予TSH抑制疗法(口服左甲状腺素钠片,控制血清TSH水平低于0.1mU/L),两组患者均给予治疗1个月。比较两组患者治疗前后血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平及外周血CD3^+、CD4^+、CD8^+水平。结果:两组治疗前的血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平比较,均无显著性差异(P>0.05);两组治疗后的血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平相比治疗前均较低,且实验组治疗后血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平变化均显著优于对照组(P<0.05)。两组治疗前的外周血CD3^+、CD4^+、CD8^+水平比较,均无显著性差异(P>0.05);两组治疗后的外周血CD3^+、CD4^+水平相比治疗前均较高、CD8^+水平相比治疗前均较低,且实验组治疗后血外周血CD3^+、CD4^+、CD8^+水平变化均优于对照组,具有显著性差异(P<0.05)。结论:DTC行甲状腺全切手术治疗后接受TSH抑制疗法能够有效降低血清Tg、VEGF、TSGF、CD44V6、sIL-2R水平,改善细胞免疫功能,值得在临床上推广应用。

Autocrine IL-8 Contributes to Propionibacterium Acnes-induced Proliferation and Differentiation of HaCaT Cells via AKT/FOXO1/Autophagy

Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.

乙型慢性活动性肝炎患者外周血淋巴细胞亚群白细胞介素-2受体的初探

应用间接免疫荧光法,放射免疫分析法,微量细胞培养法及斑点杂交技术,检测了27例乙型慢性活动性肝炎(CAH-B)患者及7例正常对照者CD4-、CD8-及B细胞膜上白细胞介素-2受体(mIL-2R,CD26抗原为其β链),各亚群细胞培养上清及病人同期血清中可溶性白细胞介素-2受体(sIL-2R),CD4-细胞培养上清中IL-2活性。结果CAH-B病人外周血,CD25抗原阳性的CD4+、CD8+细胞及B细胞较正常对照者减少,且CD25抗原阳性的CD4+、CD8+细胞减少较B细胞明显;CD4+细胞培养上清中IL-2活性较正常人降低,并与病情的轻重、CD4-细胞mIL-2R的表达呈正相关;CAH-B病人血清sIL-2R增高,但培养上清sIL-2R与正常对照无显著性差异。结果提示CAH-B病人外周血CD4+、CD8+及B细胞mIL-2R表达均减弱;CAH-B病人体内T细胞免疫应答功能受损可能较B细胞受损明显;CAH-B病人体内IL-2产生水平低下与病情轻重有某种关联;CAH-B患者血清中增高的sIL-2R可能来自肝内浸润的免疫活性细胞mIL-2Rβ链脱落。

mIL-2R,T cell subsets & hepatitis C

AIM: To study the levels of membrane interleukin-2 receptor (mIL-2R) and T cell subsets in peripheral blood mononuclear cells (PBMC) from patients with hepatitis C and their role in the pathogenesis of hepatitis C. METHODS: The levels of mIL-2R and T cells subsets in PBMC were detected by biotin- streptatividin (BSA) technique before and after stimulation with PHA in 203 patients with hepatitis C with HCV-RNA(+), anti-HCV(+), anti-HCV(-). RESULTS: The total expressive levels of mIL-2R before and after stimulation with PHA(0.03+/-0.01, 0.03+/-0.02, 0.04+/-0.02, 0.36+/-0.03), and T cell subsets in PBMC (0.62+/-0.06, 0.37+/-0.05, 0.35+/-0.07) were all lower in patients with hepatitis C than those in normal controls (0.66+/-0.07, 0.41+/-0.06, 0.31+/-0.05, P【0.01). Among the patients, the levels of mIL-2R were lower in silence than those in situation of PHA inducting (P【0.01). However, the levels of mIL-2R were similar in acute hepatitis C to that in chronic hepatitis C (P】0.05). The levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+) were lower and CD(8)(+) was higher in patients with acute and chronic hepatitis C with anti-HCV(+) than those in normal controls (0.62+/-0.06, 0.37+/-0.05, 0.35+/-0.07, 1.18+/-0.30, 0.61+/-0.07, 0.37+/-0.05, 1.39+/-0.33, 0.31+/-0.05, P【0.05-P【0.01). CONCLUSION: The cellular immunity is obviously changed in patients with hepatitis C. The levels of mIL-2R and activation of T cells are closely associated with chronicity of hepatitis C.