title: An unusual pro-inflammatory role of interleukin-10 induced by arabinosylated lipoarabinomannan in murine peritoneal macrophages.
abstract: Various species of Mycobacteria produce a major cell wall-associated lipoglycan, called Lipoarabinomannan (LAM), which is involved in the virulence of Mycobacterial species. In this study, we tried to establish the role of the increased IL-10 secretion under Arabinosylated-LAM (Ara-LAM) treatment, the LAM that induces apoptosis in host macrophages or PBMC. We have studied the survival and apoptotic factors by western blotting, and estimated nitrite generation by Griess reaction, quantified iNOS mRNA by semi-quantitative RT-PCR, and ultimately the fate of the cells were studied by Flow Cytometric Analysis of AnnexinV-FITC binding. As per our observations, neutralization of released IL-10 in C57BL/6 peritoneal macrophages prior to Ara-LAM treatment, as well as macrophages from IL-10 knockout (KO) mice treated with Ara-LAM, showed significant down regulation of pro-apoptotic factors and up regulation of survival factors. These effects were strikingly similar to those when peritoneal macrophages were subjected to TNF-alpha and IL-12 neutralization followed by Ara-LAM-treatment. However, under similar conditions virulent Mannosylated-LAM (from Mycobacterium tuberculosis) treatment of macrophages clearly depicts the importance of IL-10 in the maintenance of pathogenesis, proving its usual immunosuppressive role. Thus, from our detailed investigations we point out an unusual pro-inflammatory action of IL-10 in Ara-LAM treated macrophages, where it behaves in a similar manner as the known Th1 cytokines TNF- alpha and IL-12.
authors.affiliation: Department of Microbiology, Bose Institute, P1/12 CIT Scheme VII M, Kolkata, India.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Majumder
authors.forename: Ranadhir
authors.initials: R
authors.lastname: Dey
authors.forename: Ram Kumar
authors.initials: RK
authors.lastname: Mathur
authors.forename: Sriparna
authors.initials: S
authors.lastname: Datta
authors.forename: Madhumita
authors.initials: M
authors.lastname: Maitra
authors.forename: Sanjukta
authors.initials: S
authors.lastname: Ghosh
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; C050016:lipoarabinomannan; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II