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Here we show that murine primary PMCs constitutively express TLR-1 through TLR-9 and, upon activation with peptidoglycan (PGN), mouse PMC produce antimicrobial peptide \u03b2-defensin-2 (mBD-2). Treatment of PMCs with staphylococcal PGN, a gram-positive bacterial cell wall component and a TLR-2 agonist, resulted in a significant increase in TLR-2 and mBD-2 expression. Silencing of TLR-2 expression by small interfering RNA led to the downregulation of PGN-induced mBD-2 expression, thereby establishing causal relationship between the activation of TLR-2 receptor and mBD-2 production. PMCs exposed to PGN showed increased p38 MAPK activity. In addition, PGN-induced mBD-2 expression was attenuated by SB203580, a p38 MAPK inhibitor, underlining the importance of p38 MAPK in mBD-2 induction. Inhibition of erk1\/erk2 or phosphatidylinositol 3-kinase did not block PGN-induced mBD-2 expression in PMC. PGN-activated PMC-derived mBD-2 significantly killed Staphylococcus aureus, and mBD-2-neutralizing antibodies blunted this antimicrobial activity. Taken together, these data indicate that PMCs may contribute to host innate immune defense upon exposure to gram-positive bacteria or their products within the pleural space by upregulating TLR-2 and mBD-2 expression.<\/jats:p>","DOI":"10.1152\/ajplung.00276.2007","type":"journal-article","created":{"date-parts":[[2008,7,12]],"date-time":"2008-07-12T01:09:50Z","timestamp":1215824990000},"page":"L461-L470","source":"Crossref","is-referenced-by-count":33,"title":["Innate immune responses in murine pleural mesothelial cells: Toll-like receptor-2 dependent induction of \u03b2-defensin-2 by staphylococcal peptidoglycan"],"prefix":"10.1152","volume":"295","author":[{"given":"Tajamul","family":"Hussain","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najmunnisa","family":"Nasreen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimu","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan F.","family":"Bellew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veena B.","family":"Antony","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal A.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(03)00007-0"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.103.3.839"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00403902"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1378\/chest.99.5.1162"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1378\/chest.113.3.788"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Bals R, Goldman MJ, Wilson JM.Mouse beta-defensin 1 is a salt-sensitive antimicrobial peptide present in epithelia of the lung and urogenital tract.Infect Immun66: 1225\u20131232, 1998.","DOI":"10.1128\/IAI.66.3.1225-1232.1998"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Bals R, Wang X, Meegalla RL, Wattler S, Weiner DJ, Nehls MC, Wilson JM.Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs.Infect Immun67: 3542\u20133547, 1999.","DOI":"10.1128\/IAI.67.7.3542-3547.1999"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-200211000-00013"},{"key":"R9","unstructured":"Carmody RJ, Chen YH.Nuclear factor-kappaB: activation and regulation during Toll-like receptor signaling.Cell Mol Immunol4: 31\u201341, 2007."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1034\/j.1398-9995.2003.00180.x"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.005389"},{"key":"R12","unstructured":"Donowitz G, Mandell GL.Acute pneumonia. 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