NF-{kappa}B Is Required Within the Innate Immune System to Inhibit Microflora-Induced Colitis and Expression of IL-12 p40

• Published in: The Journal of immunology (1950) 2003-08, Vol.171 (3), p.1484-1492
• Main Authors: Tomczak, Michal F, Erdman, Susan E, Poutahidis, Theofilos, Rogers, Arlin B, Holcombe, Hilda, Plank, Benjamin, Fox, James G, Horwitz, Bruce H
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

We have previously presented evidence demonstrating that mice deficient in NF-[kappa]B subunits are susceptible to colitis induced by the pathogenic enterohepatic Helicobacter species, H. hepaticus. However, it has not been determined whether NF-[kappa]B is required within inhibitory lymphocyte populations, within cells of the innate immune system, or both, to suppress inflammation. To examine these issues, we have performed a series of adoptive transfer experiments using recombination-activating gene (Rag)-2 super(-/-) or p50 super(-/-)p65 super(+/-)Rag-2 super(-/-) mice as hosts for wild-type (WT) and p50 super(-/- )p65 super(+/-) lymphocyte populations. We have shown that although the ability of H. hepaticus to induce colitis in Rag-2 super(-/-) mice is inhibited by the presence of either WT or p50 super(-/-)p65 super(+/-) splenocytes, these splenocyte populations are unable to suppress H. hepaticus-induced colitis in p50 super(-/- )p65 super(+/-)Rag-2 super(-/-) mice. Colitis in these animals is characterized by increased expression of inflammatory cytokines including IL-12 p40, and depletion of IL-12 p40 from p50 super(-/-)p65 super(+/-) mice ameliorates H. hepaticus-induced disease. Consistent with a primary defect in the regulation of IL-12 expression, H. hepaticus induced markedly higher levels of IL-12 p40 in p50 super(-/-)p65 super(+/-) macrophages than in WT macrophages. These results suggest that inhibition of H. hepaticus-induced IL-12 p40 expression by NF-[kappa]B subunits is critical to preventing colonic inflammation in response to inflammatory microflora.