title: Mycobacterium indicus pranii downregulates MMP-9 and iNOS through COX-2 dependent and TNF-α independent pathway in mouse peritoneal macrophages in vitro.
abstract: Despite the popular belief that granulomas are innate immune mechanism to restrict mycobacterial growth, evidences suggest that granulomas facilitate growth of Mycobacterium by recruiting large numbers of uninfected macrophages to the site of infection. Matrix metalloproteinase-9 (MMP-9) has been shown to be directly involved in recruitment of macrophages at the site of infection, contributing to nascent granuloma maturation and bacterial growth. In this manuscript it is reported that heat-killed Mycobacterium indicus pranii (MIP) leads to a significant downregulation of MMP-9 in murine peritoneal macrophages in vitro. The downregulation of MMP-9 is mediated through cyclooxygenase-2 (COX-2), but independent of tumor necrosis factor-α (TNF-α). By limiting nuclear to cytoplasmic export of COX-2 and iNOS transcripts, MIP inhibits excessively-high levels of nitric oxide which can be damaging to the host during acute phases of infection. MIP has been shown to provide clinical improvement in all phases of leprosy and used for treatment of leprosy and tuberculosis.
authors.affiliation: School of Biotechnology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Rajeev Kumar
authors.initials: RK
authors.lastname: Pandey
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Dahiya
authors.forename: Ajit
authors.initials: A
authors.lastname: Sodhi
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D034443:RNA Transport / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9