Mycobacterium avium complex activates nuclear factor kappa B via inductionof 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 immun e response. In this study, we demonstrate that proinflammatory cytokines su ch as tumor necrosis factor alpha (TNF alpha) produced upon activation by t he 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 bi nding activity was not detected until 90 to 120 min postinfection. Supershi ft analysis revealed increased p50 in the MAC-induced NF-kappa B binding co mplexes. Consistent with an autocrine mechanism, anti-TNF alpha antibody an d dexamethasone, a known cytokine inhibitor, both completely suppressed the effect of MAC on the induction of NF-kappa B, Taken together, these findin gs suggest that exposure of monocyte cell membranes to MAC induces endogeno us 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 MA C infection. (C) 1999 Academic Press.