title: Beta-arrestin 1 is involved in the catabolic response stimulated by hyaluronan degradation in mouse chondrocytes.
abstract: Beta-arrestin-1 (β-arrestin-1) is an adaptor protein that functions in the termination of G-protein activation and seems to be involved in the mediation of the inflammatory response. Interleukin-1β (IL-1β) elicits the expression of inflammatory mediators through a mechanism involving hyaluronan (HA) degradation, thereby contributing to toll-like receptor 4 (TLR-4) and CD44 activation. Stimulation of both receptors induces nuclear factor kappaB (NF-kB) activation that, through transforming-growth-factor-activated-kinase-1 (TAK-1), in turn stimulates the inflammatory mediators of transcription. As β-arrestin-1 seems to play an inflammatory role in arthritis, we have investigated the involvement of β-arrestin-1 in a model of IL-1β-induced inflammatory response in mouse chondrocytes. IL-1β treatment significantly increases chondrocytes TLR-4, CD44, β-arrestin-1, TAK-1, and serine/threonine kinase (AKT) mRNA expression and related protein levels. NF-kB is also markedly activated with consequent tumor-necrosis-factor-alpha, interleukin-6, and inducible-nitric-oxide-synthase up-regulation. Treatment of IL-1β-stimulated chondrocytes with β-arrestin-1 and/or AKT and/or TAK-1-specific inhibitors significantly reduces all parameters, although the inhibitory effect exerted by TAK-1-mediated pathways is more effective than that of β-arrestin-1. β-Arrestin-1-induced NF-kB activation is mediated by the AKT pathway as shown by IL-1β-stimulated chondrocytes treated with AKT inhibitor. Finally, a specific HA-blocking peptide (Pep-1) has confirmed the inflammatory role of degraded HA as a mediator of the IL-1β-induced activation of β-arrestin-1.
authors: Department of Biomedical Sciences and Morphological and Functional Images, Section of Medical Biotechnologies and Preventive Medicine, School of Medicine (Policlinico Universitario), University of Messina, Torre Biologica, 5° Piano, Via C. Valeria, 98125, Messina, Italy, gcampo@unime.it.
authors: Giuseppe M
authors: GM
authors: Campo
authors: Angela
authors: A
authors: Avenoso
authors: Angela
authors: A
authors: D'Ascola
authors: Michele
authors: M
authors: Scuruchi
authors: Alberto
authors: A
authors: Calatroni
authors: Salvatore
authors: S
authors: Campo
mesh_terms: D000818:Animals; D019390:Arrestins / Q000276:immunology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology*; D006820:Hyaluronic Acid / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000276:immunology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605255:Arrb1 protein, mouse; D019390:Arrestins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D006820:Hyaluronic Acid