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

IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial-mesenchymal transition (EMT).
Int J Clin Exp Pathol. 2013;6(8):1481-92
Authors: Ji X, Li J, Xu L, Wang W, Luo M, Luo S, Ma L, Li K, Gong S, He L, Zhang Z, Yang P, Zhou Z, Xiang X, Wang CY
Abstract
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 ...

Source: International Journal of Clinical and Experimental Pathology - August 9, 2013 Category: Pathology Authors: Ji X, Li J, Xu L, Wang W, Luo M, Luo S, Ma L, Li K, Gong S, He L, Zhang Z, Yang P, Zhou Z, Xiang X, Wang CY Tags: Int J Clin Exp Pathol Source Type: research