{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:17:30Z","timestamp":1791267450804,"version":"4.1.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>Legionella pneumophila is an important causative agent of severe pneumonia in humans. Human alveolar epithelium is an effective barrier for inhaled microorganisms and actively participates in the initiation of innate host defense. Induction of antimicrobial peptide human \u03b2-defensin-2 (hBD-2) by various stimuli in epithelial cells has been reported. However, the mechanisms by which bacterial infections enhance hBD-2 expression remain poorly understood. In this study, we investigated the effect of the pulmonary pathogen L. pneumophila on induction of hBD-2 in human pulmonary epithelial cells. Infection with L. pneumophila markedly increased hBD-2 production, and the response was attenuated in Toll-like receptor (TLR) 2 and TLR5 transient knockdown cells. Furthermore, pretreatment with SB-202190 (an inhibitor of p38 MAPK) and JNK II (an inhibitor of c-Jun NH<jats:sub>2<\/jats:sub>-terminal kinase), but not U0126 (an inhibitor of ERK), reduced L. pneumophila-induced hBD-2 release in A549 cells. L. pneumophila-induced hBD-2 liberation was mediated via recruitment of NF-\u03baB and AP-1 to the hBD-2 gene promoter. Additionally, we showed that exo- and endogenous hBD-2 elicited a strong antimicrobial effect towards L. pneumophila. Together, these results suggest that L. pneumophila induces hBD-2 release in A549 cells, and the induction seems to be mediated through TLR2 and TLR5 as well as activation of p38 MAPK, JNK, NF-\u03baB, and AP-1.<\/jats:p>","DOI":"10.1152\/ajplung.00365.2009","type":"journal-article","created":{"date-parts":[[2010,2,13]],"date-time":"2010-02-13T02:51:10Z","timestamp":1266029470000},"page":"L687-L695","source":"Crossref","is-referenced-by-count":50,"title":["Induction of human \u03b2-defensin-2 in pulmonary epithelial cells by<i>Legionella pneumophila<\/i>: involvement of TLR2 and TLR5, p38 MAPK, JNK, NF-\u03baB, and AP-1"],"prefix":"10.1152","volume":"298","author":[{"given":"Stefanie","family":"Scharf","sequence":"first","affiliation":[{"name":"Department of Internal Medicine\/Infectious Diseases and Pulmonary Medicine, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hippenstiel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Infectious Diseases and Pulmonary Medicine, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Flieger","sequence":"additional","affiliation":[{"name":"FG11 Division of Bacterial Infections, Robert Koch-Institut, Wernigerode, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Suttorp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Infectious Diseases and Pulmonary Medicine, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe Dje","family":"N'Guessan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Infectious Diseases and Pulmonary Medicine, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3810\/pgm.2001.05.933"},{"key":"B2","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1128\/IAI.67.7.3542-3547.1999","volume":"67","author":"Bals R","year":"1999","journal-title":"Infect Immun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01489-07"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2004.10.002"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/15687"},{"key":"B6","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1128\/JCM.23.6.1121-1126.1986","volume":"23","author":"Edelstein PH","year":"1986","journal-title":"J Clin Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46913-0"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00212"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00305.x"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/43088"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031220"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.102681"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/01902140701756687"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-97"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/thorax.58.5.425"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.06.049"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401850"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.1.316"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2005.07.006"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80005-3"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(98)00480-6"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2008.05.019"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00100.2006"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604638200"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4505-4511.2005"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256652"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.3.1401"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.2.940"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00141005"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.07899.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2003-0388OC"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01145.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200306000-00002"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00171908"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.8.2871-2882.2003"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5398"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511044200"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0616fje"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.10.5750-5758.2004"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700020"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.3.1512-1518.2004"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1202941"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902140"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.525"}],"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.00365.2009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T23:09:38Z","timestamp":1590620978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00365.2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":44,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,5]]}},"alternative-id":["10.1152\/ajplung.00365.2009"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00365.2009","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5]]}}}