Nicotine induces the secretion of TGF-β1 and FGF-2 via HMGB1/RAGE in human airway epithelial cells

Objective To test whether nicotine induces the secretion of transforming growth factor-β1 (TGF-β1)and fibroblast growth factor 2 (FGF-2) in HBECs in vitro via the high mobility group protein B1 (HMGB1)/receptor for advanced glycation end products (RAGE) signaling pathway. Methods Cultured HBECs were exposed to nicotine (6×10-6 mol/L) for 24 h. The secretion of HMGB1, TGF-β1 and FGF-2 was assessed by ELISA, the expression of RAGE was assessed by Western blotting.HBECs were either transfected with a small interfering RNA (siRNA) targeting HMGB1 for 48 h or incubated with anti-RAGE antibodies for 1 h and subsequently stimulated with nicotine for 24 h, then the secretion of HMGB1, TGF-β1 and FGF-2 was assessed by ELISA, the expression of RAGE was assessed by Western blotting. Results We showed that cells exposed to nicotine for 24 h exhibited significantly increased HMGB1, TGF-β1 and FGF-2 secretion and RAGE expression.The HMGB1 siRNA prevented these effects.Furthermore, anti-RAGE antibodies significantly decreased the secretion of TGF-β1 and FGF-2 from HBECs. Conclusions These results suggest that nicotine induces the secretion of TGF-β1 and FGF-2 in HBECs via the HMGB1/RAGE signaling pathway. Key words: Nicotine; Transforming growth factor beta1; Fibroblast growth factor 2; Human bronchial epithelial cells; High mobility group protein B1/Receptor for advanced glycation end products