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We investigated the role of GSK-3 in the secretion of chemokines and growth factors by human airway smooth muscle cells after exposure to cigarette smoke extract (CSE) or interleukin-1\u03b2 (IL-1\u03b2), important factors involved in the development of COPD. Cultured human airway smooth muscle cells were exposed to increasing concentrations of CSE (1\u201315%) and IL-1\u03b2 (0.01\u20131.0 ng\/ml), which induced the secretion of VEGF-A and IL-8, whereas eotaxin secretion was induced by IL-1\u03b2 only. Inhibition of GSK-3 by the selective inhibitor SB216763 or CHIR\/CT99021 attenuated the cytokine and growth factor release induced by CSE and\/or IL-1\u03b2, without affecting the basal release. Secretion of the cytokines by airway smooth muscle partially depends on NF-\u03baB signaling, and GSK-3 has been implicated in regulating multiple steps in activating the NF-\u03baB signaling pathway. IL-1\u03b2 treatment induced degradation of the NF-\u03baB inhibitory protein I\u03ba-B\u03b1 followed by nuclear translocation and DNA binding of p65 NF-\u03baB, which were unaffected by inhibition of GSK-3. However, induction of NF-\u03baB-dependent transcriptional activity by IL-1\u03b2 and CSE was largely reduced upon GSK-3 inhibition by SB216763. Collectively, we demonstrate that CSE and IL-1\u03b2 activate airway smooth muscle cells to secrete the proinflammatory cytokines IL-8, eotaxin, and VEGF-A. Furthermore, we show that GSK-3 regulates the release of these cytokines induced by CSE and IL-1\u03b2 by promoting NF-\u03baB-dependent gene transcription.<\/jats:p>","DOI":"10.1152\/ajplung.00232.2010","type":"journal-article","created":{"date-parts":[[2011,3,19]],"date-time":"2011-03-19T03:18:18Z","timestamp":1300504698000},"page":"L910-L919","source":"Crossref","is-referenced-by-count":20,"title":["Glycogen synthase kinase-3 regulates cigarette smoke extract- and IL-1\u03b2-induced cytokine secretion by airway smooth muscle"],"prefix":"10.1152","volume":"300","author":[{"given":"Hoeke A.","family":"Baarsma","sequence":"first","affiliation":[{"name":"Departments of 1Molecular Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman","family":"Meurs","sequence":"additional","affiliation":[{"name":"Departments of 1Molecular Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Halayko","sequence":"additional","affiliation":[{"name":"Departments of Physiology and Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Menzen","sequence":"additional","affiliation":[{"name":"Departments of 1Molecular Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Departments of 1Molecular Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huib A. 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