TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulates cellular proliferation, angiogenesis, inflammmation, and apoptosis. In this study, we investigated the effect of TWEAK on human bronchial epithelial cells. A human bronchial epithelial cell line, BEAS2B, expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced IL-8 and GM-CSF upon TWEAK stimulation in a dose-dependent manner, which was abrogated by anti-Fn14 blocking antibody. TWEAK induced phosphorylation of IkappaBalpha and BAY11-7082, a selective inhibitor of IkappaBalpha. phosphorylation, inhibited the TWEAK-induced IL-8 and GM-CSF production by BEAS2B cells. Moreover, primary Cultured human bronchial epithelial cells also expressed Fn14 and produced IL-8 and GM-CSF upon TWEAK stimulation. Collectively, TWEAK stimulated human bronchial epithelial cells to produce IL-8 and GNI-CSF through Fn14. Because IL-8 and GNI-CSF are associated with inflammatory conditions, these results suggest that TWEAK/Fn14 interaction may play sonic roles in airway inflammatory responses. (C) 2004 Elsevier Inc. All rights reserved.