TY - JOUR AB - Airway smooth muscle cells (ASMC) are a source of inflammatory chemokines that may propagate airway inflammatory responses. We investigated the production of the CXC chemokine growth-related oncogene protein-? (GRO-?) from ASMC induced by cytokines and the role of MAPK and NF-?B pathways. ASMC were cultured from human airways, grown to confluence, and exposed to cytokines IL-1? and TNF-? after growth arrest. GRO-? release, measured by ELISA, was increased by >50-fold after IL-1? (0.1 ng/ml) or 5-fold after TNF-? (1 ng/ml) in a dose- and time-dependent manner. GRO-? release was not affected by the T helper type 2 cytokines IL-4, IL-10, and IL-13. IL-1? and TNF-? also induced GRO-? mRNA expression. Supernatants from IL-1?-stimulated ASMC were chemotactic for neutrophils; this effect was inhibited by anti-GRO-? blocking antibody. AS-602868, an inhibitor of IKK-2, and PD-98059, an inhibitor of ERK, inhibited GRO-? release and mRNA expression, whereas SP-600125, an inhibitor of JNK, reduced GRO-? release without effect on mRNA expression. SB-203580, an inhibitor of p38 MAPK, had no effect. AS-602868 but not PD-98059 or SP-600125 inhibited p65 DNA-binding induced by IL-1? and TNF-?. By chromatin immunoprecipitation assay, IL-1? and TNF-? enhanced p65 binding to the GRO-? promoter, which was inhibited by AS-602868. IL-1?- and TNF-?-stimulated expression of GRO-? from ASMC is regulated by independent pathways involving NF-?B activation and ERK and JNK pathways. GRO-? released from ASMC participates in neutrophil chemotaxis. Copyright © 2006 the American Physiological Society. AU - Issa, R AU - Xie, S AU - Lee, KY AU - Stanbridge, RD AU - Bhavsar, P AU - Sukkar, MB AU - Chung, KF DA - 2006/07/12 DO - 10.1152/ajplung.00384.2005 JO - American Journal of Physiology - Lung Cellular and Molecular Physiology PY - 2006/07/12 TI - GRO-? regulation in airway smooth muscle by IL-1? and TNF-?: Role of NF-?B and MAP kinases VL - 291 Y1 - 2006/07/12 Y2 - 2024/03/29 ER -