Short Thymic Stromal Lymphopoietin Attenuates Toluene Diisocyanate-induced Airway Inflammation and Inhibits High Mobility Group Box 1-Receptor for Advanced Glycation End Products and Long Thymic Stromal Lymphopoietin Expression
Short Thymic Stromal Lymphopoietin Attenuates Toluene Diisocyanate-induced Airway Inflammation and Inhibits High Mobility Group Box 1-Receptor for Advanced Glycation End Products and Long Thymic Stromal Lymphopoietin Expression
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短胸腺基质淋巴细胞生成素可减轻甲苯二异氰酸酯诱导的气道炎症，并抑制晚期糖基化终产物的高迁移率族盒 1 受体和长胸腺基质淋巴细胞生成素表达
DOI：
10.1093/toxsci/kfx043
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发表时间：
2017
影响因子：
3.8
通讯作者：
Zhao Haijin
中科院分区：
文献类型：
--
作者：
Wang Yanhong;Le Yanqing;Zhao Wenqu;Lin Yun;Wu Yue;Yu Changhui;Xiong Jing;Zou Fei;Dong Hangming;Cai Shaoxi;Zhao Haijin
短胸腺基质淋巴生成素(Short TSLP)是TSLP的变异体之一，在内毒素休克和结肠炎小鼠模型中具有抗炎活性。我们最新的工作报告说，短的TSLP可以防止屋尘螨引起的上皮屏障破坏。然而，短TSLP在甲苯二异氰酸酯(TDI)诱导的哮喘中的作用尚不清楚。用TDI致敏和激发雄性BALB/c小鼠建立化学致敏哮喘模型。在每次挑战前，给合成的短TSLP多肽进行鼻腔或腹膜注射。TDI显著增加气道炎症和高反应性，而TSLP短期治疗可抑制这些炎症和高反应性。TDI组小鼠气道上皮和全肺组织中TSLP、高迁移率族蛋白1(HMGB1)和晚期糖基化终产物受体(RAGE)的水平均显著高于对照组，给予短TSLP后显著降低。在体外，TDI-人血清白蛋白(HSA)和重组人(Rh)HMGB1均能促进人支气管上皮细胞(16HBE)长TSLP基因的产生，但不能促进短TSLP基因的产生。与单独用TDI-HSA或rhHMGB1刺激相比，经短TSLP处理的细胞RAGE和长TSLP的表达减少，Akt(S473)、p38MAPK(T180/Y182)和STAT5(Y694)的磷酸化水平降低。结果提示，短TSLP可抑制化学致敏哮喘模型的气道炎症，其机制可能与抑制HMGB1-RAGE和长TSLP的表达及抑制STAT5(Y694)的磷酸化有关。
Short thymic stromal lymphopoietin (short TSLP), one of TSLP variants, exerts anti-inflammatory activities in endotoxin shock and colitis mouse models. Our latest work reported that short TSLP prevented house dust mite-induced epithelial barrier disruption. Yet the role of short TSLP in toluene diisocyanate (TDI)-induced asthma is unknown. Male BALB/c mice were sensitized and challenged with TDI to generate a chemical-induced asthma model. Synthetic short TSLP peptides were given intranasally or intraperitoneally before each challenge. TDI significantly increased inflammation and hyperresponsiveness of airway, which were suppressed by short TSLP treatment. Levels of mouse TSLP, high mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) in airway epithelium and whole lung tissues were markedly increased in TDI group compared with control mice, which were decreased after administration of short TSLP. Meanwhile, short TSLP also inhibited STAT5(Y694) phosphorylation, which was highly expressed in airways of TDI-exposure mice.In vitro, both TDI-human serum albumin (HSA) and recombinant human (rh) HMGB1 promoted long TSLP but not short TSLP gene production in human bronchial epithelial cells (16HBE). Cells pre-treated with short TSLP exhibited less expression of RAGE and long TSLP and lower phosphorylation of Akt(S473), p38 MAPK(T180/Y182), and STAT5(Y694) than stimulated with TDI-HSA or rhHMGB1 alone. Results suggest that short TSLP prevents airway inflammation in a chemical-induced asthma model, which might be associated with the inhibitions of HMGB1-RAGE and long TSLP expression and STAT5(Y694) phosphorylation.