title: β-Arrestin-1 deficiency protects mice from experimental colitis.
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.
authors: Division of Human Pathology, Department of Physiology, Michigan State University, East Lansing, Michigan, USA.
authors: Taehyung
authors: T
authors: Lee
authors: Eunhee
authors: E
authors: Lee
authors: Regina
authors: R
authors: Irwin
authors: Peter C
authors: PC
authors: Lucas
authors: Laura R
authors: LR
authors: McCabe
authors: Narayanan
authors: N
authors: Parameswaran
mesh_terms: D000818:Animals; D019390:Arrestins / Q000172:deficiency* / Q000378:metabolism; D003092:Colitis / Q000097:blood / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control*; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; C000605255:Arrb1 protein, mouse; D019390:Arrestins; D015850:Interleukin-6; D016328:NF-kappa B; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases
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