{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:19:39Z","timestamp":1790378379073,"version":"4.1.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2015,10,15]]},"abstract":"<jats:p>There is rising interest in how obesity affects respiratory diseases, since epidemiological findings indicate a strong relationship between the two conditions. Leptin is a potent adipokine produced mainly by adipocytes. It regulates energy storage and expenditure and also induces inflammation. Previous studies have shown that leptin is able to activate inflammatory cells such as lymphocytes and granulocytes, but little is known about its effect on lung structural cells. The present study investigated the effects of leptin on human airway epithelial cells by using human primary airway epithelial cells and a human airway epithelial cell line, BEAS-2B. Flow cytometry showed enhanced ICAM-1 expression by both of those cells in response to leptin, and that effect was abrogated by dexamethasone or NF-\u03baB inhibitor. Flow cytometry and quantitative PCR showed that airway epithelial cells expressed leptin receptor (Ob-R), whose expression level was downregulated by leptin itself. Multiplex cytokine analysis demonstrated enhanced production of CCL11, G-CSF, VEGF, and IL-6 by BEAS-2B cells stimulated with leptin. Furthermore, transfection of Ob-R small interference RNA decreased the effect of leptin on CCL11 production as assessed by quantitative PCR. Finally, leptin induced migration of primary airway epithelial cells toward leptin, suppressed BEAS-2B apoptosis induced with TNF-\u03b1 and IFN-\u03b3, and enhanced proliferation of primary airway epithelial cells. In summary, leptin was able to directly activate human airway epithelial cells by binding to Ob-R and by NF-\u03baB activation, resulting in upregulation of ICAM-1 expression, induction of CCL11, VEGF, G-CSF, and IL-6 synthesis, induction of migration, inhibition of apoptosis, and enhancement of proliferation.<\/jats:p>","DOI":"10.1152\/ajplung.00365.2014","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:54:11Z","timestamp":1567990451000},"page":"L801-L811","source":"Crossref","is-referenced-by-count":35,"title":["Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells"],"prefix":"10.1152","volume":"309","author":[{"given":"Maho","family":"Suzukawa","sequence":"first","affiliation":[{"name":"National Hospital Organization Tokyo National Hospital, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikiya","family":"Koketsu","sequence":"additional","affiliation":[{"name":"Nishikobe Medical Center, Kobe, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayaka","family":"Igarashi","sequence":"additional","affiliation":[{"name":"National Hospital Organization Tokyo National Hospital, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nagase","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Matsutani","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Shoji","sequence":"additional","affiliation":[{"name":"National Hospital Organization Tokyo National Hospital, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hebisawa","sequence":"additional","affiliation":[{"name":"National Hospital Organization Tokyo National Hospital, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Ohta","sequence":"additional","affiliation":[{"name":"National Hospital Organization Tokyo National Hospital, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.04.032"},{"key":"B2","doi-asserted-by":"crossref","first-page":"55633","DOI":"10.1074\/jbc.M409825200","volume":"279","author":"Buss H","year":"2004","journal-title":"J Biol Chem"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-013-9615-1"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069297"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/382589a0"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.09.003"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.01.011"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.27.15958"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.06.009"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2014.70"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1992.03490240070039"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9148"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.16.1517"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001674"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1378\/chest.12-0872"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.5.1315"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00073.2004"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nri1350"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2737"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7205"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/29795"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1671OC"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00845.2009"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00010.2004"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1351.045"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2010.02.004"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/2.6.553"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2005.01.064"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.10.007"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055249"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.82"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004054"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(02)00078-8"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2002.282.3.L405"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00884-X"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101984"},{"key":"B37","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.4049\/jimmunol.144.12.4579","volume":"144","author":"Van Seventer GA","year":"1990","journal-title":"J Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.085423"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.1967851"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3109\/01902140903427033"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00365.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:29:03Z","timestamp":1695169743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00365.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,15]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,10,15]]}},"alternative-id":["10.1152\/ajplung.00365.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00365.2014","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,15]]}}}