β-Arrestin-1 Deficiency Protects Mice from Experimental Colitis

beta-Arrestins are intracellular scaffolding proteins that modulate specific cell signaling pathways. Recent studies, in both cell culture and in vivo models, have demonstrated an important role for beta-arrestin-1 in inflammation. However, the role of beta-arrestin-1 in the pathogenesis of inflammatory bowel disease (IBD) is not known. Our goal was to investigate the role of beta-arrestin-1 in IBD using mouse models of colitis. To this end, we subjected wild-type (WT) and beta-arrestin-1 knockout (beta-arr-1(-/-)) mice to colitis induced by trinitrobenzenesulfonic acid or dextran sulfate sodium and examined the clinical signs, gross pathology, and histopathology of the colon, as well as inflammatory components. The beta-arr-1(-/-) mice displayed significantly attenuated colitis, compared with WT mice, in both models. Consistent with the phenotypic observations, histological examination of the colon revealed attenuated disease pathology in the beta-arr-1(-/-) mice. Our results further demonstrate that beta-arr-1(-/-) mice are deficient in IL-6 expression in the colon, but have higher expression of the anti-inflammatory IL-10 family of cytokines. Our results also demonstrate diminished ERK and NF kappa B pathways in the colons of beta-arr-1(-/-) mice, compared with WT mice. Taken together, our results demonstrate that decreased IL-6 production and enhanced IL-10 and IL-22 production in beta-arrestin-1-deficient mice likely lead to attenuated gut inflammation.