TY - JOUR T1 - Signaling pathway of isophorone diisocyanate-responsive IL-8 in airway smooth muscle cells JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00192109 SP - erj01921-2009 AU - P-L. Kuo AU - M-S. Huang AU - S-K. Huang AU - W-C. Ni AU - J-Y. Hung AU - Y-C. Ko AU - C-H. Hung AU - Y-M. Tsai AU - T-H. Duh AU - Y-L. Hsu Y1 - 2010/01/01 UR - http://erj.ersjournals.com/content/early/2010/08/20/09031936.00192109.abstract N2 - This study is first to analyse the soluble factors, secreted by the bronchial epithelium after exposure to isophorone diisocyanate (IPDI), responsible for increasing migration and proliferation of primary normal human bronchial smooth muscle cells (BSMC).We treated immortalized non-tumourigenic human bronchial epithelial cells (BEAS-2B) and primary normal human bronchial epithelial cells (HBEC) with IPDI, and then collected the condition medium (IPDI-BEAS-2B-CM and IPDI-HBEC-CM), which was added to BSMC. Exposure of BEAS-2B and HBEC to IPDI increased IL-8 production. Culture of BSMC with IPDI-BEAS-2B-CM and IPDI-HBEC-CM increased BSMC proliferation and migration, which are major features in asthma remodeling. Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased FAK, Src, ERK1/2 and AKT activation. Blocking FAK by a specific inhibitor significantly decreased BSMC migration and proliferation by inhibiting ERK1/2 activation. FAK and ERK1/2 inhibitor also decreased IPDI-BEAS-2B-CM, IPDI-HBEC-CM and rhIL-8-mediated BSMC proliferation and migration, whereas blocking Rnd3 by siRNA failed to affect BSMC proliferation, suggesting that Rnd3 was only involved in the regulation of BSMC migration.Our study suggests that inhibition of IL-8 or IL-8-mediated FAK/ERK/Rnd3 signaling is an attractive therapeutic target for IPDI-mediated asthma. ER -