Beta-arrestin 1 is involved in the catabolic response stimulated by hyaluronan degradation in mouse chondrocytes.
Cell Tissue Res
; 361(2): 567-79, 2015 Aug.
Article
en En
| MEDLINE
| ID: mdl-25673209
ABSTRACT
Beta-arrestin-1 (ß-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-1ß (IL-1ß) 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 ß-arrestin-1 seems to play an inflammatory role in arthritis, we have investigated the involvement of ß-arrestin-1 in a model of IL-1ß-induced inflammatory response in mouse chondrocytes. IL-1ß treatment significantly increases chondrocytes TLR-4, CD44, ß-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-1ß-stimulated chondrocytes with ß-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 ß-arrestin-1. ß-Arrestin-1-induced NF-kB activation is mediated by the AKT pathway as shown by IL-1ß-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-1ß-induced activation of ß-arrestin-1.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arrestinas
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Condrocitos
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Interleucina-1beta
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Ácido Hialurónico
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Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Tissue Res
Año:
2015
Tipo del documento:
Article
Pais de publicación:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
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GERMANY