Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.
J Biol Chem
; 285(43): 32824-32833, 2010 Oct 22.
Article
em En
| MEDLINE
| ID: mdl-20729213
ABSTRACT
Phosphorylation is the most important post-translational event at a cellular level that is regulated by protein kinases. MAPK is a key player in the important cellular signaling pathway. It has been hypothesized that phosphorylation might have a role in the induction of break tolerance against some autoantigens such as SRP72. The aim of this study was to explore the pathways of phosphorylation and overexpression of the SRP72 polypeptide, using an in vitro model of Jurkat cells stimulated by recombinant human (rh)IL-1ß in the presence of MAPK inhibitors. We used Jurkat cells as a substrate stimulated with rhIL-1ß in the presence of MAPK inhibitors at different concentrations in a time course in vitro experiment by immunoprecipitation, immunoprecipitation-Western blotting, and real time PCR. Our results showed that rhIL-1ß causes up-regulation of protein expression and phosphorylation of SRP72 in Jurkat cells. Inhibitors of the MAPK pathway ERK1/2 or p38α/ß down-regulate the expression of SRP72 autoantigen in Jurkat cells stimulated by rhIL-1ß. Our results highlight the importance of studying the pathways of activation and overexpression of autoantigens. It will be necessary to perform careful research on various kinases pathways, including MAPK in dermatomyositis and other rheumatic diseases, to help to explain the routes of activation and inhibition of autoantigens. The understanding of this process may help to develop new therapies to prevent and control the loss of tolerance toward own normal proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Regulação para Cima
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Partícula de Reconhecimento de Sinal
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Proteína Quinase 1 Ativada por Mitógeno
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Sistema de Sinalização das MAP Quinases
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Proteína Quinase 3 Ativada por Mitógeno
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Proteínas Quinases p38 Ativadas por Mitógeno
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Inibidores de Proteínas Quinases
/
Interleucina-1beta
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article