{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:55:17Z","timestamp":1776628517218,"version":"3.51.2"},"reference-count":53,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:p>Chronic obstructive pulmonary disease (COPD) is an inflammatory disease, characterized by a progressive decline in lung function. Airway smooth muscle (ASM) mass may be increased in COPD, contributing to airflow limitation and proinflammatory cytokine production. Cigarette smoke (CS), the major risk factor of COPD, causes ASM cell proliferation, as well as interleukin-8 (IL-8)-induced neutrophilia. In various cell types, transforming growth factor-\u03b2-activated kinase 1 (TAK1) plays a crucial role in MAP kinase and NF-\u03baB activation, as well as IL-8 release induced by IL-1\u03b2, TNF-\u03b1, and lipopolysaccharide. The role of TAK1 in CS-induced IL-8 release is not known. The aim of this study was to investigate the role of TAK1 in CS-induced NF-\u03baB and MAP kinase signaling and IL-8 release by human ASM cells. Stimulation of these cells with CS extract (CSE) increased IL-8 release and ERK-1\/2 phosphorylation, as well as I\u03ba-B\u03b1 degradation and p65 NF-\u03baB subunit phosphorylation. CSE-induced ERK-1\/2 phosphorylation and I\u03ba-B\u03b1 degradation were both inhibited by pretreatment with the specific TAK1 inhibitor LL-Z-1640-2 (5Z-7-oxozeaenol; 100 nM). Similarly, expression of dominant-negative TAK1 inhibited CSE-induced ERK-1\/2 phosphorylation. In addition, inhibitors of TAK1 and the NF-\u03baB (SC-514; 50 \u03bcM) and ERK-1\/2 (U-0126; 3 \u03bcM) signaling inhibited the CSE-induced IL-8 release by ASM cells. These data indicate that TAK1 plays a major role in CSE-induced ERK-1\/2 and NF-\u03baB signaling and in IL-8 release by human ASM cells. 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