Mycobacterium avium complex activates nuclear factor κB via induction of inflammatory cytokines

A variety of microorganisms has been reported to directly induce NF-kappa B, 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 (TNF alpha) produced upon activation by the Mycobacterium avium complex (MAC) preceed NF-kappa B activity in U937, a human monocytoid cell line. MAC induction of TNF alpha mRNA expression was detected within 15 min after MAC infection, whereas enhanced NF-kappa B binding activity was not detected until 90 to 120 min postinfection. Supershift analysis revealed increased p50 in the MAC-induced NF-kappa B binding complexes. Consistent with an autocrine mechanism, anti-TNF alpha antibody and dexamethasone, a known cytokine inhibitor, both completely suppressed the effect of MAC on the induction of NF-kappa B, Taken together, these findings suggest that exposure of monocyte cell membranes to MAC induces endogenous TNF alpha, which in turn enhances NF-kappa B binding activity. The rapid induction of TNF alpha may be important in the initial host response to MAC infection. (C) 1999 Academic Press.