title: Differential regulation of type IV collagenases and metalloelastase in murine macrophages by the synthetic bacterial lipopeptide JBT 3002.
abstract: We determined whether the expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs (TIMP) in murine macrophages is regulated by the novel synthetic bacterial lipopeptide JBT 3002. Multilamellar liposomes (MLV) encapsulating JBT 3002 (MLV-JBT 3002) stimulated the production of 72-kDa and 92-kDa (gelatinase A and B) type IV collagenase and inhibited the production of murine metalloelastase (MME) in a dose-dependent manner in murine peritoneal macrophages. MLV-JBT 3002 also induced production of TIMP-1. MLV-JBT 3002 did not induce collagenase production in tumor cells. Priming murine macrophages with interferon-gamma (IFN-gamma) inhibited JBT 3002-stimulated production of both MMP-9 and MMP-2 and further inhibited production of MME by a mechanism involving nitric oxide (NO). This conclusion is based on data showing that IFN-gamma failed to inhibit production of MMP in the presence of L-methyl arginine or in macrophages from inducible nitric oxide synthase knockout mice. These data suggest that JBT 3002 differentially regulates the production of various MMPs and TIMP in macrophages.
authors.affiliation: Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.forename: K
authors.initials: K
authors.lastname: Xie
authors.forename: I
authors.initials: I
authors.lastname: Eue
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: J J
authors.initials: JJ
authors.lastname: Killion
authors.forename: I J
authors.initials: IJ
authors.lastname: Fidler
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis*; D003470:Culture Media; D003720:Densitometry; D005122:Exudates and Transudates / Q000166:cytology / Q000187:drug effects; D005260:Female; D007202:Indicators and Reagents; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D003470:Culture Media; D007202:Indicators and Reagents; C112524:JBT-3002; D055666:Lipopeptides; D008074:Lipoproteins; D008081:Liposomes; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D009569:Nitric Oxide; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12