{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:19:02Z","timestamp":1783635542105,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of Taiwan","award":["MOST 107-2314-B-436-001"],"award-info":[{"award-number":["MOST 107-2314-B-436-001"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["109-2314-B-038-095-MY3"],"award-info":[{"award-number":["109-2314-B-038-095-MY3"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["DP2-108-21121-T-01-04"],"award-info":[{"award-number":["DP2-108-21121-T-01-04"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["MKC111R02"],"award-info":[{"award-number":["MKC111R02"]}]},{"name":"Ministry of Education of Taiwan","award":["MOST 107-2314-B-436-001"],"award-info":[{"award-number":["MOST 107-2314-B-436-001"]}]},{"name":"Ministry of Education of Taiwan","award":["109-2314-B-038-095-MY3"],"award-info":[{"award-number":["109-2314-B-038-095-MY3"]}]},{"name":"Ministry of Education of Taiwan","award":["DP2-108-21121-T-01-04"],"award-info":[{"award-number":["DP2-108-21121-T-01-04"]}]},{"name":"Ministry of Education of Taiwan","award":["MKC111R02"],"award-info":[{"award-number":["MKC111R02"]}]},{"name":"MacKay Junior College of Medicine, Nursing, and Management","award":["MOST 107-2314-B-436-001"],"award-info":[{"award-number":["MOST 107-2314-B-436-001"]}]},{"name":"MacKay Junior College of Medicine, Nursing, and Management","award":["109-2314-B-038-095-MY3"],"award-info":[{"award-number":["109-2314-B-038-095-MY3"]}]},{"name":"MacKay Junior College of Medicine, Nursing, and Management","award":["DP2-108-21121-T-01-04"],"award-info":[{"award-number":["DP2-108-21121-T-01-04"]}]},{"name":"MacKay Junior College of Medicine, Nursing, and Management","award":["MKC111R02"],"award-info":[{"award-number":["MKC111R02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Toll-like receptor (TLR) is essential for the immune response to Mycobacterium tuberculosis (MTB) infection. However, the mechanism whereby TLR mediates the MTB-induced pleural mesothelial hyperpermeability in tuberculous pleural effusion (TBPE) remains unclear. Pleural effusion size and pleural fluid levels of vascular endothelial growth factor (VEGF) and soluble TLR2 (sTLR2) in patients with TBPE (n = 36) or transudative pleural effusion (TPE, n = 16) were measured. The effects of MTB H37Ra (MTBRa) on pleural mesothelial permeability and the expression of VEGF and zonula occludens (ZO)-1 in human pleural mesothelial cells (PMCs) were assessed. Levels of VEGF and sTLR2 were significantly elevated in TBPE compared to TPE. Moreover, effusion VEGF levels correlated positively, while sTLR2 values correlated negatively, with pleural effusion size in TBPE. In human PMCs, MTBRa substantially activated JNK\/AP-1 signaling and upregulated VEGF expression, whereas knockdown of TLR2 remarkably inhibited MTBRa-induced JNK phosphorylation and VEGF overexpression. Additionally, both MTBRa and VEGF markedly reduced ZO-1 expression and induced pleural mesothelial permeability, while TLR2 silencing or pretreatment with anti-VEGF antibody significantly attenuated the MTBRa-triggered effects. Collectively, TLR2 mediates VEGF overproduction and downregulates ZO-1 expression in human PMCs, leading to mesothelial hyperpermeability in TBPE. Targeting TLR2\/VEGF pathway may confer a potential treatment strategy for TBPE.<\/jats:p>","DOI":"10.3390\/ijms24032846","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T02:21:12Z","timestamp":1675304472000},"page":"2846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Toll-like Receptor 2 Mediates VEGF Overexpression and Mesothelial Hyperpermeability in Tuberculous Pleural Effusion"],"prefix":"10.3390","volume":"24","author":[{"given":"Wei-Lin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Ling","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"Lai","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Heng","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hsin","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-976X","authenticated-orcid":false,"given":"Chi-Li","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan"},{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1185449","article-title":"The population dynamics and control of tuberculosis","volume":"328","author":"Dye","year":"2010","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4046\/trd.2014.76.4.153","article-title":"Tuberculous pleurisy: An update","volume":"76","author":"Jeon","year":"2014","journal-title":"Tuberc. 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