Regulation of TGF-β1-induced connective tissue growth factor expression in airway smooth muscle cells

Transforming growth factor (TGF)-β may play an important role in airway remodeling, and the fibrogenic effect of TGF-β may be mediated through connective tissue growth factor (CTGF) release. We investigated the role of MAPKs and phosphatidylinositol 3-kinase (PI3K) and the effects of inflammatory cytokines on TGF-β-induced CTGF expression in human airway smooth muscle cells (ASMC). We examined whether Smad signal was involved in the regulatory mechanisms. TGF-β1 induced a time- and concentration-dependent expression of CTGF gene and protein as analyzed by real-time RT-PCR and Western blot. Inhibition of ERK and c-jun NH2-terminal kinase (JNK), but not of p38 MAPK and PI3K, blocked the effect of TGF-β1 on CTGF mRNA and protein expression and on Smad2/3 phosphorylation. T helper lymphocyte 2-derived cytokines, IL-4 and IL-13, attenuated TGF-β1-stimulated mRNA and protein expression of CTGF and inhibited TGF-β1-stimulated ERK1/2 and Smad2/3 activation in ASMC. The proinflammatory cytokines tumor necrosis fac...