{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:10:48Z","timestamp":1772626248616,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3164,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The elevated levels of inflammatory cytokines such as tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and interleukin\u20101\u03b2 (IL\u20101\u03b2) have been found in the fluid of airways in symptomatic asthmatics. These cytokines have been considered as mitogens to stimulate cell proliferation in tracheal smooth muscle cells (TSMCs). We therefore investigated the effects of TNF\u2010\u03b1 and IL\u20101\u03b2 on cell proliferation and activation of p42\/p44 mitogen\u2010activated protein kinase (MAPK) in these cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TNF\u2010\u03b1 and IL\u20101\u03b2 induced [<jats:sup>3<\/jats:sup>H]\u2010thymidine incorporation in a time\u2010 and concentration\u2010dependent manner. The maximal stimulation of [<jats:sup>3<\/jats:sup>H]\u2010thymidine incorporation induced by TNF\u2010\u03b1 and IL\u20101\u03b2 was seen 12\u2003h after incubation with these cytokines.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In response to TNF\u2010\u03b1 and IL\u20101\u03b2, p42\/p44 MAPK was activated with a concentration\u2010dependent manner in TSMCs. Pretreatment of TSMCs with pertussis toxin did not change DNA synthesis and phosphorylation of MAPK induced by TNF\u2010\u03b1 and IL\u20101\u03b2. These responses were attenuated by a tyrosine kinase inhibitor herbimycin, a phosphatidyl choline (PC)\u2010phospholipase C (PLC) inhibitor D609, a phosphatidyl inositide (PI)\u2010PLC inhibitor U73122, a protein kinase C inhibitor staurosporine, and removal of Ca<jats:sup>2+<\/jats:sup> by addition of BAPTA\/AM plus EGTA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>TNF\u2010\u03b1\u2010 and IL\u20101\u03b2\u2010induced [<jats:sup>3<\/jats:sup>H]\u2010thymidine incorporation and phosphorylation of p42\/p44 MAPK was completely inhibited by PD98059 (an inhibitor of MEK1\/2), indicating that activation of MEK1\/2 was required for these responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that the mitogenic effects of TNF\u2010\u03b1 and IL\u20101\u03b2 were mediated through the activation of MEK1\/2 and p42\/p44 MAPK pathway. TNF\u2010\u03b1\u2010 and IL\u20101\u03b2\u2010mediated responses were modulated by PLC, Ca<jats:sup>2+<\/jats:sup>, PKC, and tyrosine kinase associated with cell proliferation in TSMCs.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>130<\/jats:bold>, 891\u2013899; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703359\">10.1038\/sj.bjp.0703359<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703359","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:14:42Z","timestamp":1106946882000},"page":"891-899","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Tumour necrosis factor\u2010\u03b1\u2010 and interleukin\u20101\u03b2\u2010stimulated cell proliferation through activation of mitogen\u2010activated protein kinase in canine tracheal smooth muscle cells"],"prefix":"10.1111","volume":"130","author":[{"given":"Chuen\u2010Mao","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shue\u2010Fen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan\u2010Chwan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi\u2010Tso","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin\u2010Sung","family":"Chien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih\u2010Chung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Der","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.46.27489"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.15.1.8679222"},{"key":"e_1_2_7_4_1","first-page":"687","article-title":"Relationship between smooth muscle volume and contractile response in airway tissue. 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