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Because bradykinin (BK) and interleukin (IL)-6 may play important roles in the regulation of airway inflammation, we tested whether BK induces IL-6 expression from human ASM cells. BK stimulates IL-6 release in a concentration-dependent (0.001\u201310 \u03bcM) and time-dependent (2\u201324 h) manner. The increases in IL-6 protein and total mRNA were inhibited by the selective B2 receptor antagonist HOE-140 but not by the selective B1 receptor antagonist desArg9(Leu8)-BK. Actinomycin D (a transcription inhibitor), dexamethasone, indomethacin, IL-4, and IL-13 (Th2 type cytokines) inhibited the expression of IL-6 by BK. In contrast, BK-induced IL-6 secretion was enhanced by exogenous prostaglandin E2 and salmeterol. Using immunoblot analysis, we showed that BK activates ERK1\/2 and p38 mitogen-activated protein kinases (MAPK). Blocking ERK1\/2 with PD98059 or p38 MAPK with SB203580 reduced BK-induced IL-6 expression. BK also activates luciferase activity in ASM cells transfected with a reporter plasmid containing AP-1 enhancer elements. BK-induced, AP-1\u2013dependent transcription was inhibited by indomethacin and dexamethasone. Curcumin, an inhibitor of AP-1, also reduced BK-induced IL-6 expression. These data show that BK, via the B2 receptor, induces IL-6 expression in ASM cells by involving ERK1\/2 and p38 MAPK signaling pathways and the AP-1 transcription factor. Moreover, IL-6 secretion by BK is sensitive to corticosteroids and is regulated by Th2-derived cytokines.<\/jats:p>","DOI":"10.1165\/rcmb.2002-0040oc","type":"journal-article","created":{"date-parts":[[2003,2,19]],"date-time":"2003-02-19T19:35:10Z","timestamp":1045683310000},"page":"330-338","source":"Crossref","is-referenced-by-count":52,"title":["Bradykinin Induces Interleukin-6 Production in Human Airway Smooth Muscle Cells"],"prefix":"10.1093","volume":"28","author":[{"given":"Chien-Da","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan; and Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Tliba","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan; and Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Reynold A.","family":"Panettieri","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan; and Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Amrani","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan; and Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,3,1]]},"reference":[{"key":"2026030623532606700_BIB1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1136\/thx.47.11.979","volume":"47","year":"1992","journal-title":"Thorax"},{"key":"2026030623532606700_BIB2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1146\/annurev.pa.32.040192.002455","volume":"32","year":"1992","journal-title":"Ann. 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