Control of IFN-αA by CD73: Implications for Mucosal Inflammation

摘要: Inflammatory diseases influence tissue metabolism, altering regulation of extracellular adenine nucleotides, with a resultant protective adenosine. Ecto-5′-nucleotidase (CD73) is central surface enzyme generating Thus, we hypothesized that CD73 in mucosal inflammation as modeled by trinitrobenzene sulfonate (TNBS) colitis. Initial studies revealed >3-fold induction mRNA levels after TNBS Additionally, the severity colitis was increased, determined weight loss and colonic shortening, cd73 −/− mice relative to +/+ controls. Likewise, enteral administration selective inhibitor α,β-methylene ADP resulted similar increase Gene array profiling cytokine expression, verified real-time PCR, >90% down-regulation IFN-αA ADP-treated mice, compared mice. Exogenous recombinant partially protected TNBS-treated Cytokine increases both IFN-γ TNF-α colitic animals, independent genotype. However, IL-10 increased wild-type on day 3 administration, whereas mounted no response. This response restored exogenous IFN-αA. Further this preceded transient 2 exposure. Together, these indicate critical regulatory role for CD73-modulated IFNαA acute inflammatory phase colitis, thereby implicating element adenosine signaling during inflammation.