Galectin-9及其受体Tim-3 在哮喘小鼠肺组织中的表达

张志英; 栾斌; 冯晓霞

PDF(1194 KB)

中国当代儿科杂志 ›› 2011, Vol. 13 ›› Issue (5) : 406-410.

论著·实验研究

Galectin-9及其受体Tim-3 在哮喘小鼠肺组织中的表达

张志英，栾斌，冯晓霞

作者信息 +

Expression of Galectin-9 and Tim-3 in lungs of mice with asthma

ZHANG Zhi-Ying, LUAN Bin, FENG Xiao-Xia

Author information +

文章历史 +

摘要

目的：探讨半乳糖凝集素-9（Galectin-9）及其受体T 细胞免疫球蛋白粘蛋白分子-3（Tim-3）在哮喘小鼠肺组织中的表达及 PPAR-γ激动剂罗格列酮（ROS）对其表达的影响。方法45 只清洁级雌性 BALB/c 小鼠随机分为对照组、哮喘组、ROS干预组。观察卵清蛋白激发及ROS干预治疗后哮喘小鼠肺组织的病理变化；应用 RT-PCR 方法检测肺组织 Galectin-9 和 Tim-3 mRNA 的表达；采用酶联免疫吸附测定法检测外周血 IL-4 及 IFN-γ的表达水平。结果哮喘组肺组织 Galectin-9 和 Tim-3 mRNA 表达显著高于对照组及 ROS 干预组（P<0.05）。哮喘组外周血 IL-4 的表达量较对照组及 ROS 组明显升高，而 IFN-γ表达量较对照组及 ROS 组明显降低（P<0.05）。Galectin-9 和 Tim-3 mRNA 表达量与 IL-4 呈正相关（r=0.792，0.794，P<0.05），与 IFN-γ呈负相关（r=-0.692，-0.757，P<0.05）。结论哮喘小鼠气道肺组织中 Galectin-9 和 Tim-3 mRNA 表达有明显升高，并且其改变与 Th1/Th2 细胞因子表达量具有相关性，ROS干预治疗后 Galectin-9 和 Tim-3 mRNA 表达下调。

Abstract

OBJECTIVE: To study the expression of Galectin-9 and Tim-3 in lungs of mice with asthma and the effect of rosiglitazone (PPAR-γ agonist) on their expression. METHODS: Fortyfive BALB/c SPF female mice were randomized into control group and asthma groups with and without rosiglitazone intervention. After ovalbumin stimulation and rosiglitazone intervention the pathological changes of the lung tissues were observed. Galectin-9 and Tim-3 mRNA levels in lung tissues were determined using RT-PCR. The levels of IL-4 and IFN-γ in peripheral blood were measured using ELISA. RESULTS: The expression of Galectin-9 and Tim-3 mRNA of lung tissues in the untreated asthma group increased significantly compared with the control and the rosiglitazone treated groups (P<0.05). A significantly increased blood expression of IL-4 and a significantly decreased blood expression of IFN-γ were found in the untreated asthma group compared with the control and the rosiglitazone-treated groups (P<0.05). The expression of Galectin-9 and Tim-3 mRNA was positively correlated with blood IL-4 level (r=0.792, r=0.794 respectively; P<0.05), but negatively correlated with blood IFN-γ level (r=-0.692, r=-0.757 respectively; P<0.05). CONCLUSIONS: Galectin-9 and Tim-3 mRNA levels in lungs increase in mice with asthma and significantly correlate with the levels of blood Th1/Th2 cytokines. This suggests that Galectin-9 and Tim-3 are closely related to inflammatory process in asthma. Rosiglitazone treatment may decrease the expression of Galectin-9 and Tim-3.

导出引用

张志英，栾斌，冯晓霞. Galectin-9及其受体Tim-3 在哮喘小鼠肺组织中的表达[J]. 中国当代儿科杂志. 2011, 13(5): 406-410

ZHANG Zhi-Ying, LUAN Bin, FENG Xiao-Xia. Expression of Galectin-9 and Tim-3 in lungs of mice with asthma[J]. Chinese Journal of Contemporary Pediatrics. 2011, 13(5): 406-410

中图分类号： R-33

参考文献

［1］李峰，赵红洋，温暖，毕玫荣，吴蕾，朱微微.支气管哮喘发病机制进展［J］.实用全科医学，2007，5（10）922-923.

［2］Katoh S, Ishii N, Nobumoto A, Takeshita K, Dai SY, Shinonaga R, et al. Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of allergic asthma［J］. Am J Respir Crit Care Med, 2007, 176(1): 27-35.

［3］沈华浩,王苹莉.支气管哮喘小鼠模型应用评价［J］.中华结核和呼吸杂志,2005,28(4):284-286.

［4］田代印，符州，张燕，王莉佳，迟磊，李睿，等.一种改良型小鼠哮喘模型方法的建立及评价［J］.重庆医科大学学报,2005,30(4):601-603.

［5］韩伟，周新.过氧化物酶体增殖物活化受体γ在支气管哮喘小鼠血管重塑中的作用［J］.中华结核和呼吸杂志,2006,29(7):484-488.

［6］栾斌，黄先杰，乔俊英. SDF-1及CXCR4在哮喘小鼠肺组织中的表达及布地奈德的干预作用［J］.中国当代儿科杂志，2010,12（3）：215-218.

［7］Hamid Q.Inflammatory cells, cytokine and chemokine expression in asthma immunocytochemistry and in situ hybridization［J］.Allergy Clin Immunol,2003,111(4):902-903.

［8］Suk K, Hwang DY, Lee MS.Natural autoantibody to galectin-9 in normal human sera［J］. J Clin Immunol, 1999, 19(3): 158-165.

［9］Yamamoto H, Kashio Y, Shoji H, Shinonaga R, Yoshimura T, Nishi N, et al. Involvement of galectin-9 in guinea pig allergic airway inflammation［J］.Int Arch Allergy Immunol, 2007, 143（Suppl 1）: 95-105.

［10］Chae SC, Park YR, Lee JH, Chung HT. The association of TIM-3 gene polymorphism with atopic disease in Korean population［J］.Hum Immunol, 2004, 65(12): 14271431.

［11］Mclntire JJ, Umetsu SE, Akbari O, Potter M, Kuchroo VK, Barsh GS, et al. Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family［J］. Nat Immunol, 2001, 2(12): 1109-1116.

［12］Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ. et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity［J］. Nat Immunol, 2005, 6 (12): 1245-1252.

［13］Zhu C, Anderson AC, Kuchroo VK. Tim-3 and its regulatory role in Immune Responses［J］.Curr Top Microbiol Immunol, 2011, 350: 1-15.

［14］Kearley J, McMillan SJ, Lloyd CM. Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti-Tim-3 antibody in vivo［J］.J Exp Med, 2007, 204(6): 1289-1294.

［15］Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, et al. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappa B and AP-1［J］.Biol Chem, 1999, 274（45）:32048-32054.

［16］Wang AC, Dai X, Luu B,Conrad DJ. Peroxisome proliferator-activated receptor-gamma regulates airway epithelial cell activation［J］.Am J Respir Cell Mol Biol, 2001, 24（6）:688-693.

［17］Serhan CN, Devchand PR.Novel antiinflammatory targets for asthma. A role for PPARgamma?［J］. Am J Respir Cell Mol Biol, 2001, 24(6): 658-661.

［18］Fukui N, Honda K, Ito E, Ishikawa K. Peroxisome proliferator-activated receptor γ negatively regulates allergic rhinitis in Mice［J］. Allergol lnt, 2009, 58(2): 247-253.

［19］Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model［J］. J Allergy Clin Immunol, 2004, 113（5）:882-888.

［20］Patel HJ, Belvisi MG, Bishop-Bailey D, Yacoub MH, Mitchell JA. Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior antiinflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy［J］. J Immunol, 2003, 170(5): 2663-2669.

［21］Woerly G, Honda K, Loyens M, Papin JP, Auwerx J, Staels B, et al. Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammatory and eosinophil activation［J］.Exp Med, 2003, 198(3): 411-421.