title: Mannosylated lipoarabinomannan balances apoptosis and inflammatory state in mycobacteria-infected and uninfected bystander macrophages.
abstract: To assess the role of mannosylated lipoarabinomannan (ManLAM) in the inflammatory and apoptotic response of mycobacteria-infected and uninfected, bystander cells we applied a mouse macrophage model of infection with avirulent strains--Mycobacterium bovis BCG, Mycobacterium tuberculosis (MTB) H37Ra and compared with a virulent MTB H37Rv strain infection. ManLAM contributed to the infection of macrophages by protection from apoptosis with stabilized Bcl-2 expression and down-regulated Bax expression for infected cells (BCG) or with stabilized Bcl-2 expression for uninfected bystander target cells (H37Ra). Additionally, ManLAM up-regulated FasL expression on the infected cells. Active extracellular signal-regulated kinase (ERK1/2) in BCG and H37Rv infection provided an anti-apoptotic effect by stabilization of anti-apoptotic Bcl-2 expression in the infected cells. Inhibitors specific for c-Jun-NH2-terminal kinase or stress-activated kinase (JNK) and p38 kinase decreased apoptosis of infected cells (BCG, H37Ra) and of uninfected bystanders (H37Ra) by down-regulating Bax. ManLAM significantly down-regulated production of pro-inflammatory IL-12 and TNF-alpha and activation of JNK by both avirulent strains. We conclude that by stabilization of Bcl-2 expression, down-regulation of JNK activity and down-regulation of pro-inflammatory cytokines production ManLAM can contribute to suppression of apoptosis and inflammatory reaction of uninfected, bystander cells.
authors: Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences-SGGW, Ciszewskiego 8, 02-786 Warsaw, Poland.
authors: Bartosz
authors: B
authors: Wojtas
authors: Beata
authors: B
authors: Fijalkowska
authors: Adam
authors: A
authors: Wlodarczyk
authors: Ada
authors: A
authors: Schollenberger
authors: Marek
authors: M
authors: Niemialtowski
authors: Beston
authors: B
authors: Hamasur
authors: Andrzej
authors: A
authors: Pawlowski
authors: Malgorzata
authors: M
authors: Krzyzowska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000472:pathogenicity*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014774:Virulence; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; C050016:lipoarabinomannan; D048031:JNK Mitogen-Activated Protein Kinases