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We hypothesized that MMPs are elevated in bronchoalveolar lavage fluid of tuberculosis patients and that antimycobacterial agents may have a modulatory effect on MMP secretion. Concentrations of MMP-1, -2, -3, -7, -8, and -9 were elevated in the bronchoalveolar lavage fluid from tuberculosis patients compared to those in bronchoalveolar lavage fluid from patients with other pulmonary conditions. There was a positive correlation between MMP-3, MMP-7, and MMP-8 and a chest radiological score of cavitation and parenchymal damage. Respiratory epithelial cell-derived MMP-3 was suppressed by moxifloxacin, rifampicin, and azithromycin in a dose-dependent manner. Respiratory epithelial cell-derived MMP-1 was suppressed by moxifloxacin and azithromycin, whereas MMP-9 secretion was only decreased by moxifloxacin. In contrast, moxifloxacin and azithromycin both increased MMP-1 and -3 secretion from MRC-5 fibroblasts, demonstrating that the effects of these drugs are cell specific. Isoniazid did not affect MMP secretion. In conclusion, MMPs are elevated in bronchoalveolar lavage fluid from tuberculosis patients and correlate with parameters of tissue destruction. Antimycobacterial agents have a hitherto-undescribed immunomodulatory effect on MMP release by stromal cells.<\/jats:p>","DOI":"10.1128\/aac.02141-13","type":"journal-article","created":{"date-parts":[[2014,6,3]],"date-time":"2014-06-03T06:12:01Z","timestamp":1401775921000},"page":"4657-4665","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Antimycobacterial Drugs Modulate Immunopathogenic Matrix Metalloproteinases in a Cellular Model of Pulmonary Tuberculosis"],"prefix":"10.1128","volume":"58","author":[{"given":"Shivani","family":"Singh","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunity, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Kubler","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Utpal K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Tuberculosis Unit, Department of Medicine and Paediatrics, Nalanda University Hospitals, Agam Kuan, Patna, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Singh","sequence":"additional","affiliation":[{"name":"Tuberculosis Unit, Department of Medicine and Paediatrics, Nalanda University Hospitals, Agam Kuan, Patna, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Gardiner","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajniti","family":"Prasad","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Banaras Hindu University, Varanasi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Elkington","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity, Imperial College London, London, United Kingdom"},{"name":"Clinical and Experimental Sciences, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon S.","family":"Friedland","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.051979"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1538"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm763"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1418"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.2002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.52.6.502"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2007.02.009"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2003.08.014"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.3.2001073"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.1997.tb04525.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4223"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001847"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57423"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45666"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201110-1769OC"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1179663"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"3936","DOI":"10.4049\/jimmunol.163.7.3936","article-title":"Pulmonary epithelial cells are a source of IL-8 in the response to Mycobacterium tuberculosis: essential role of IL-1 from infected monocytes in a NF-kappa B-dependent network","volume":"163","author":"Wickremasinghe MI","year":"1999","unstructured":"WickremasingheMIThomasLHFriedlandJS. 1999. 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