IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial-mesenchymal transition (EMT)

International Journal of Clinical and Experimental Pathology

Keng Li¹  Long He¹  Ming Luo¹  Shuangling Luo¹  Libing Ma¹  Zhiguang Zhou¹  Xudong Xiang¹  Ping Yang¹  Subo Gong¹  Jinxiu Li¹  Cong-Yi Wang¹  Wenjing Wang¹  Zhijun Zhang¹  Xiaoying Ji¹  Li Xu¹ 

关键词: Severe asthma;    airway remodeling;    chronic inflammatory milieu;    epithelial mesenchymal transition (EMT);    ERK1/2;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Severe asthma is a chronic airway disease characterized by the Th2/Th17-polarized inflammation along with permanent airway remodeling. Despite past extensive studies, the exact role for Th2 and Th17 cytokines in asthmatic pathoetiology, particularly in the pathogenesis of bronchial epithelial-mesenchymal transition (EMT), is yet to be fully addressed. We herein conducted studies in 16-HBE cells and demonstrated that Th2-derived IL-4 and Th17-derived IL-17A provide a chronic inflammatory milieu that favors TGF-β₁ to induce bronchial EMT. A synergic action was noted between TGF-β₁, IL-4 and IL-17A in terms of induction of EMT. IL-4 and IL-17A synergized with TGF-β₁ to induce epithelial cells re-entering cell cycle, and to promote epithelial to mesenchymal morphological transistion, and by which they enhanced the capacity of TGF-β₁ to suppress E-cadherin expression, and to induce a-SMA expression in epithelial cells. Mechanistic studies revealed that this synergic action is coordinated by the regulation of ERK1/2 activity. Our results not only provide a novel insight into the understanding of the mechanisms underlying airway remodeling in asthmatic condition, but also have the potential for developing more effective therapeutic strategies against severe asthmatics in clinical settings.

【 授权许可】

Unknown