转化生长因子β1在呼吸道感染中的抗炎机理

Anti-inflammation mechanisms of transforming growth factor β1 in experimental respiratory tract infection

摘要:

目的：探索转化生长因子β1（transforming growth factor ?茁1，TGF?茁1）的信号通路与呼吸道感染性炎症反应的关系以及对呼吸系统免疫功能的影响。方法：采用2级符合清洁动物标准的BACB/C小鼠建立铜绿假单胞菌感染模型，以LY364947 （4-[3-（2-嘧啶基）-1氢-吡唑-4-基]-喹啉） 阻断TGF?茁1，在TGF?茁1阻断和非阻断状态下观察感染动物模型的炎症反应以及肺组织的病理变化，同时以Western blot分析细胞因子CD4和CD8含量的变化。结果：阻断TGF?茁1后，小鼠肺组织中p38激酶的磷酸化减至对照组10%以下，实验动物感染模型的炎症有所增强，CD4水平显著升高（P=0.004），而CD8的水平无显著变化。结论：TGF?茁1在呼吸道感染的炎症反应中具有抑制性调节作用，TGF?茁1阻断可能会使呼吸道感染的免疫调节功能有所增强。

Abstract:

Objective：To investigate the relationship between transforming growth factor β1（TGFβ1） signaling pathway and respiratory tract infection induced inflammation and to explore the effects of TGFβ1 on immunological function of respiratory system. Methods：BACB/C mice fulfilling grade Ⅱ clean animal criteria were artificially infected with pseudomonas aeruginosa while TGFβ1 was blocked with LY364947（4-[3-（2-pyridinyl）-1H-pyrazol-4-yl]-quinoline）. Inflammation reactions of the infected mice and pathologi－cal changes of pulmonary tissue were histochemically evaluated when TGFβ1 was blocked and unblocked respectively. CD4 and CD8 levels were tested through Western blot. Results：Blocking of TGFβ1 obviously blunted the phosphorylation of p38（10% lower than the control levels），significantly intensified the inflammation reaction and increased the CD4 levels but didn’t affect CD8 levels. Conclusions：TGFβ1 has inhibitory effect on respiratory tract infection induced inflammation and TGFβ1 blockers may enhance the immune regulation of respiratory tract infection.