title: Mycobacterium avium complex activates nuclear factor kappaB via induction of inflammatory cytokines.
abstract: A variety of microorganisms has been reported to directly induce NF-kappaB, a critical step in the regulation of genes involved in the cellular immune response. In this study, we demonstrate that proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) produced upon activation by the Mycobacterium avium complex (MAC) preceed NF-kappaB activity in U937, a human monocytoid cell line. MAC induction of TNFalpha mRNA expression was detected within 15 min after MAC infection, whereas enhanced NF-kappaB binding activity was not detected until 90 to 120 min postinfection. Supershift analysis revealed increased p50 in the MAC-induced NF-kappaB binding complexes. Consistent with an autocrine mechanism, anti-TNFalpha antibody and dexamethasone, a known cytokine inhibitor, both completely suppressed the effect of MAC on the induction of NF-kappaB. Taken together, these findings suggest that exposure of monocyte cell membranes to MAC induces endogenous TNFalpha, which in turn enhances NF-kappaB binding activity. The rapid induction of TNFalpha may be important in the initial host response to MAC infection.
authors.affiliation: Department of Medicine, University of Illinois, Chicago, Illinois, 60612, USA. ghassemi@uic.edu
authors.forename: M
authors.initials: M
authors.lastname: Ghassemi
authors.forename: B R
authors.initials: BR
authors.lastname: Andersen
authors.forename: K A
authors.initials: KA
authors.lastname: Roebuck
authors.forename: M F
authors.initials: MF
authors.lastname: Rabbi
authors.forename: J M
authors.initials: JM
authors.lastname: Plate
authors.forename: R M
authors.initials: RM
authors.lastname: Novak
mesh_terms: D019898:Autocrine Communication; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology*; D015269:Mycobacterium avium Complex / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells