{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T19:51:27Z","timestamp":1785009087346,"version":"3.55.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pulmonary cavitation is vital to the persistence and spread of Mycobacterium tuberculosis (MTb), but mechanisms underlying this lung destruction are poorly understood. Fibrillar type I collagen provides the lung\u2019s tensile strength, and only matrix metalloproteinases (MMPs) can degrade it at neutral pH. We investigated MTb-infected lung tissue and found that airway epithelial cells adjacent to tuberculosis (Tb) granulomas expressed a high level of MMP-1 (interstitial collagenase). Conditioned media from MTb-infected monocytes (CoMTb) up-regulated epithelial cell MMP-1 promoter activity, gene expression, and secretion, whereas direct MTb infection did not. CoMTb concurrently suppressed tissue inhibitor of metalloprotease-1 (TIMP-1) secretion, further promoting matrix degradation, and in Tb patients very low TIMP-1 expression was detected. MMP-1 up-regulation required synergy between TNF-\u03b1 and G protein-coupled receptor signaling pathways. CoMTb stimulated p38 MAPK phosphorylation, and this is the point of TNF-\u03b1 synergy with G protein-coupled receptor activation. Furthermore, p38 phosphorylation was the switch up-regulating MMP-1 activity and decreasing TIMP-1 secretion. Activated p38 localized to MMP-1-secreting airway epithelial cells in Tb patients. These data reveal a monocyte-epithelial cell network whereby MTb may drive tissue destruction, and they demonstrate that p38 phosphorylation is a key regulatory point in the generation of a matrix-degrading phenotype.<\/jats:p>","DOI":"10.4049\/jimmunol.175.8.5333","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:28:35Z","timestamp":1398032915000},"page":"5333-5340","source":"Crossref","is-referenced-by-count":97,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    Up-Regulates Matrix Metalloproteinase-1 Secretion from Human Airway Epithelial Cells via a p38 MAPK Switch"],"prefix":"10.1093","volume":"175","author":[{"given":"Paul T G","family":"Elkington","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny E","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D C","family":"Lopez-Pascua","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia M","family":"O\u2019Kane","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna E","family":"Horncastle","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon S","family":"Friedland","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,10,15]]},"reference":[{"key":"2026020212204216200_R1","first-page":"677","volume-title":"J. 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