{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:23:25Z","timestamp":1773203005302,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"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":[[2017,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tuberculosis (TB) causes disease worldwide, and multidrug resistance is an increasing problem. Matrix metalloproteinases (MMPs), particularly the collagenase MMP-1, cause lung extracellular matrix destruction, which drives disease transmission and morbidity. The role in such tissue damage of the stromelysin MMP-10, a key activator of the collagenase MMP-1, was investigated in direct Mycobacterium tuberculosis (Mtb)\u2013infected macrophages and in conditioned medium from Mtb-infected monocyte\u2013stimulated cells. Mtb infection increased MMP-10 secretion from primary human macrophages 29-fold, whereas Mtb-infected monocytes increased secretion by 4.5-fold from pulmonary epithelial cells and 10.5-fold from fibroblasts. Inhibition of MMP-10 activity decreased collagen breakdown. In two independent cohorts of patients with TB from different continents, MMP-10 was increased in both induced sputum and bronchoalveolar lavage fluid compared with control subjects and patients with other respiratory diseases (both P\u2009&amp;lt;\u20090.05). Mtb drove 3.5-fold greater MMP-10 secretion from human macrophages than the vaccine strain bacillus Calmette\u2013Guerin (P\u2009&amp;lt;\u20090.001), whereas both mycobacteria up-regulated TNF-\u03b1 secretion equally. Using overlapping, short, linear peptides covering the sequence of early secretory antigenic target-6, a virulence factor secreted by Mtb, but not bacillus Calmette\u2013Guerin, we found that stimulation of human macrophages with a single specific 15\u2013amino acid peptide sequence drove threefold greater MMP-10 secretion than any other peptide (P\u2009&amp;lt;\u20090.001). Mtb-driven MMP-10 secretion was inhibited in a dose-dependent manner by p38 and extracellular signal\u2013related kinase mitogen-activated protein kinase blockade (P\u2009&amp;lt;\u20090.001 and P\u2009&amp;lt;\u20090.01 respectively), but it was not affected by inhibition of NF-\u03baB. In summary, Mtb activates inflammatory and stromal cells to secrete MMP-10, and this is partly driven by the virulence factor early secretory antigenic target-6, implicating it in TB-associated tissue destruction.<\/jats:p>","DOI":"10.1165\/rcmb.2016-0162oc","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T16:20:27Z","timestamp":1474474827000},"page":"223-232","source":"Crossref","is-referenced-by-count":25,"title":["Early Secretory Antigenic Target-6 Drives Matrix Metalloproteinase-10 Gene Expression and Secretion in Tuberculosis"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2608-4444","authenticated-orcid":false,"given":"Sara","family":"Brilha","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunity, Imperial College London, London, United Kingdom"},{"name":"Centre for Inflammation and Tissue Repair, Respiratory Medicine, University College London, London, United 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