P eroxisome proliferators-activated receptor gamma-agonists inhibis the expression of phosphorylation of signal transducer and activator of transcription 6 in T-lymphocytes of patients with acute asthma in vitro_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YANG Haihua , WANG Wenjun ,  XIANG Xudong , CHEN Ping , HUANG Ling , DENG Junwei

Department of Respiratory Medicine，2nd Hospital of Xiangya，Central South University.Changsha，Hunan，410011，ChinaCorresponding author：XIANG Xu-dong，E-mail：xudongxiang-2005@yahoo.com.cn;

Corresponding author：

XIANG Xudong, Email: xudongxiang-2005@yahoo.com.cn

Keywords：

Asthma; T-lymphocyte; Peroxisome proliferators-activated receptor gamma; Agonists; Rosiglitazone; Phosphorylation of signal transducer and activator of transcription-6

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Objective To explore the possible anti-inflammatory mechanism of peroxisome proliferators-activated receptor（PPAR） gamma-agonists by investigating the effects of Rosiglitazone on the expression of phosphorylation of signal transducer and activator of transcription 6（p-STAT6） and the secretion of interleukin（IL）-4 in T-lymphocytes from patients with acute asthma.Method s Peripheral blood T-lymphocytes from 10 healthy volunteers（group A） and 10 patients with acute asthma were isolated，purificated and cultured.T-lymphocytes from the asthma patients were divided into a control group（group B） and a Rosiglitazone treated group（group C）.Rosiglitazone was added with a single dose of 10-4 mol/L at 0 hour of cultrue.After cultured for 48 hours，the concentration of IL-4 in supernatant of each groups were detected by ELISA.The express of p-STAT6 in the T-lymphocytes were determined by Western blot and immunohistochemical techniques.Results The levels of IL-4 were increased markedly in group B than those in group A and group C[（170.34±9.05）pg/mL vs（76.82±7.06）pg/mL and（123.59±8.70）pg/mL，both P lt;0.01]，and which in group C was significantly lower than group A（P lt;0.01）.The levels of p-STAT6 in T lymphocytes were increased markedly in group B than in group A and C[Western blot：（6.28±0.19 vs 3.07±0.18 and 4.12±0.16；immunohistochemistry：（36.58%±7.41）% vs（11.39±4.02）% and（23.92±5.8）%，all P lt;0.01），and which in group C were significantly higher than that in group B（both P lt;0.01）.There was a positive correlation between the level of p-STAT6 and IL-4（P lt;0.01）.Conclusion The levels of p-STAT6 and IL-4 in T-lymphocytes of patients with acute asthma were suppressed by Rosiglitazone in vitro.

Citation： YANG Haihua,WANG Wenjun,XIANG Xudong,CHEN Ping,HUANG Ling,DENG Junwei. P eroxisome proliferators-activated receptor gamma-agonists inhibis the expression of phosphorylation of signal transducer and activator of transcription 6 in T-lymphocytes of patients with acute asthma in vitro. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(5): 346-349. doi: Copy

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8.	Arnold R，Neumann M，König W.Peroxisome proliferator-activated receptor-gamma agonists inhibit respiratory syncytial virus-induced expression of intercellular adhesion molecule-1 in human lung epithelial cells.Immunology，2007，121：71-81.
9.	Rampino T，Ranghino A，Guidetti C，et al.Activation of PPARgamma enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes.Transpl Immunol，2007，18：32-36.
10.	Ueki S，Kato H，Kobayashi Y，et al.Anti- and proinflammatory effects of 15-deoxy-delta-prostaglandin J2（15d-PGJ2） on human eosinophil functions.Int Arch Allergy Immunol，2007，143：15-22.
11.	王文军，向旭东.过氧化物酶体增殖物激活受体对哮喘患者树突状细胞免疫调控的影响.国际呼吸杂志，2006，26：580-583.
12.	Woerly G，Honda K，Loyens M，et al.Peroxisome Prolife rator-activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation.J Exp Med，2003，198：411-421.
13.	Miyazaki Y，Tachibana H，Yamada K，et al.Inhibitory effect of peroxisome proliferator -activated receptor-gamma ligands on the expression of IgE heavy chain germLine transcripts in the human B cell line DND39.Biochem Biophys Res Commun，2002，295：547-552.
14.	Mueller C，Weaver V，Vanden Heuvel JP，et al.Peroxisome proliferator-active ted receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma.Arch Biochem Biophys，2003，418：186-196.

1. 盛青，何建猷，梁标，等.STAT6与支气管哮喘.国外医学呼吸系统分册，2004，24：12-14.
2. 中华医学会呼吸病学分会哮喘学组.中华医学会第五届全国哮喘学术会议暨中国哮喘联盟第一次大会纪要.中华内科学杂志，2007，46：513-514.
3. 中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南（支气管哮喘的定义、诊断、治疗及教育和管理方案）.中华内科杂志，2003，42：817-822.
4. 黄玲，向旭东，王文军，等.罗格列酮对支气管哮喘急性发作期患者T淋巴细胞转录因子T bet/GATA3表达的调控.中华结核和呼吸杂志，2007，30：116-120.
5. 赵鹰，弓清梅，田新瑞，等.STAT6 ASODN对哮喘小鼠脾淋巴细胞影响的实验研究.中国组织化学与细胞化学杂志，2006，15：195-200.
6. Lugli SM，Feng N，Heim MH，et al. Tumor necrosis factor alpha enhances the expression of the interleukin（IL）-4 receptor alpha-chain on endothelial cells increasing IL-4 or IL-13-induced Stat6 activation.J Biol Chem，1997，272：5487-5494.
7. Nie M，Corbett L，Knox AJ，et al.Differential regulation of chemokine expression by peroxisome proliferator-activated receptor gamma agonists：interactions with glucocorticoids and beta2-agonists.J Biol Chem，2005，280：2550-2561.
8. Arnold R，Neumann M，König W.Peroxisome proliferator-activated receptor-gamma agonists inhibit respiratory syncytial virus-induced expression of intercellular adhesion molecule-1 in human lung epithelial cells.Immunology，2007，121：71-81.
9. Rampino T，Ranghino A，Guidetti C，et al.Activation of PPARgamma enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes.Transpl Immunol，2007，18：32-36.
10. Ueki S，Kato H，Kobayashi Y，et al.Anti- and proinflammatory effects of 15-deoxy-delta-prostaglandin J2（15d-PGJ2） on human eosinophil functions.Int Arch Allergy Immunol，2007，143：15-22.
11. 王文军，向旭东.过氧化物酶体增殖物激活受体对哮喘患者树突状细胞免疫调控的影响.国际呼吸杂志，2006，26：580-583.
12. Woerly G，Honda K，Loyens M，et al.Peroxisome Prolife rator-activated Receptors α and γ Down-regulate Allergic Inflammation and Eosinophil Activation.J Exp Med，2003，198：411-421.
13. Miyazaki Y，Tachibana H，Yamada K，et al.Inhibitory effect of peroxisome proliferator -activated receptor-gamma ligands on the expression of IgE heavy chain germLine transcripts in the human B cell line DND39.Biochem Biophys Res Commun，2002，295：547-552.
14. Mueller C，Weaver V，Vanden Heuvel JP，et al.Peroxisome proliferator-active ted receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma.Arch Biochem Biophys，2003，418：186-196.

Chinese Journal of Respiratory and Critical Care Medicine

P eroxisome proliferators-activated receptor gamma-agonists inhibis the expression of phosphorylation of signal transducer and activator of transcription 6 in T-lymphocytes of patients with acute asthma in vitro

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