PMID- 9614183 OWN - NLM STAT- MEDLINE DCOM- 19980710 LR - 20240214 IS - 1059-1524 (Print) IS - 1059-1524 (Linking) VI - 9 IP - 6 DP - 1998 Jun TI - Collagenase-3 induction in rat lung fibroblasts requires the combined effects of tumor necrosis factor-alpha and 12-lipoxygenase metabolites: a model of macrophage-induced, fibroblast-driven extracellular matrix remodeling during inflammatory lung injury. PG - 1411-24 AB - The mechanisms responsible for the induction of matrix-degrading proteases during lung injury are ill defined. Macrophage-derived mediators are believed to play a role in regulating synthesis and turnover of extracellular matrix at sites of inflammation. We find a localized increase in the expression of the rat interstitial collagenase (MMP-13; collagenase-3) gene from fibroblastic cells directly adjacent to macrophages within silicotic rat lung granulomas. Conditioned medium from macrophages isolated from silicotic rat lungs was found to induce rat lung fibroblast interstitial collagenase gene expression. Conditioned medium from primary rat lung macrophages or J774 monocytic cells activated by particulates in vitro also induced interstitial collagenase gene expression. Tumor necrosis factor-alpha (TNF-alpha) alone did not induce interstitial collagenase expression in rat lung fibroblasts but did in rat skin fibroblasts, revealing tissue specificity in the regulation of this gene. The activity of the conditioned medium was found to be dependent on the combined effects of TNF-alpha and 12-lipoxygenase-derived arachidonic acid metabolites. The fibroblast response to this conditioned medium was dependent on de novo protein synthesis and involved the induction of nuclear activator protein-1 activity. These data reveal a novel requirement for macrophage-derived 12-lipoxygenase metabolites in lung fibroblast MMP induction and provide a mechanism for the induction of resident cell MMP gene expression during inflammatory lung processes. FAU - Mariani, T J AU - Mariani TJ AD - Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA. mariani@biochem.wustl.edu FAU - Sandefur, S AU - Sandefur S FAU - Roby, J D AU - Roby JD FAU - Pierce, R A AU - Pierce RA LA - eng GR - P01 HL029594/HL/NHLBI NIH HHS/United States GR - R29 HL054049/HL/NHLBI NIH HHS/United States GR - F32 HL009179/HL/NHLBI NIH HHS/United States GR - HL-09179/HL/NHLBI NIH HHS/United States GR - HL-54049/HL/NHLBI NIH HHS/United States GR - R01 HL054049/HL/NHLBI NIH HHS/United States GR - HL-29594/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Biol Cell JT - Molecular biology of the cell JID - 9201390 RN - 0 (Culture Media, Conditioned) RN - 0 (Transcription Factor AP-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 27YG812J1I (Arachidonic Acid) RN - EC 1.13.11.31 (Arachidonate 12-Lipoxygenase) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Mmp13 protein, mouse) RN - EC 3.4.24.- (Mmp13 protein, rat) SB - IM MH - Animals MH - Arachidonate 12-Lipoxygenase/*metabolism MH - Arachidonic Acid/metabolism MH - Cell Line MH - Collagenases/*biosynthesis/genetics MH - Culture Media, Conditioned MH - Enzyme Induction MH - Extracellular Matrix/metabolism/physiology MH - Fibroblasts/*enzymology MH - Gene Expression MH - Kinetics MH - Lung/immunology MH - Lung Diseases/enzymology MH - Lung Injury MH - Macrophages/*metabolism MH - Matrix Metalloproteinase 13 MH - Mice MH - Models, Biological MH - Rats MH - Rats, Sprague-Dawley MH - Silicosis/enzymology MH - Transcription Factor AP-1/metabolism MH - Tumor Necrosis Factor-alpha/*metabolism PMC - PMC25362 EDAT- 1998/06/17 00:00 MHDA- 1998/06/17 00:01 CRDT- 1998/06/17 00:00 PHST- 1998/06/17 00:00 [pubmed] PHST- 1998/06/17 00:01 [medline] PHST- 1998/06/17 00:00 [entrez] AID - 0613 [pii] AID - 10.1091/mbc.9.6.1411 [doi] PST - ppublish SO - Mol Biol Cell. 1998 Jun;9(6):1411-24. doi: 10.1091/mbc.9.6.1411.