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β-Arrestin-1 deficiency protects mice from experimental colitis.

The American journal of pathology (2013-02-12)
Taehyung Lee, Eunhee Lee, Regina Irwin, Peter C Lucas, Laura R McCabe, Narayanan Parameswaran
ABSTRACT

β-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 β-arrestin-1 in inflammation. However, the role of β-arrestin-1 in the pathogenesis of inflammatory bowel disease (IBD) is not known. Our goal was to investigate the role of β-arrestin-1 in IBD using mouse models of colitis. To this end, we subjected wild-type (WT) and β-arrestin-1 knockout (β-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 β-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 β-arr-1(-/-) mice. Our results further demonstrate that β-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 NFκB pathways in the colons of β-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 β-arrestin-1-deficient mice likely lead to attenuated gut inflammation.

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Picrylsulfonic acid solution, 5 % (w/v) in H2O, BioReagent, suitable for determination of primary amines
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Picrylsulfonic acid solution, 1 M in H2O