RIP2 mediates LPS-induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte-derived dendritic cells.
Eur J Immunol
; 37(8): 2317-25, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17578844
ABSTRACT
IL-12, the critical factor for the generation of the Th1 type immune response, is produced by dendritic cells (DC) upon stimulation with LPS. Different signal pathways mediate LPS-induced expression of IL-12 and involve PI3K, MAPK and the transcription factor NF-kappaB. Here, we show that the kinase Raf is involved in the expression of IL-12 in human DC stimulated by LPS. We demonstrate that Raf regulates the expression of the IL-12 subunit p40 not via the kinase MEK, the major effector of Raf in growth factor-dependent signaling, but via the receptor-interacting protein 2 (RIP2) using specific inhibitors for MAPK pathways. RIP2 is a kinase participating in LPS/Toll-like receptor 4 signaling. Knockdown of RIP2 by siRNA inhibited LPS-dependent expression of IL-12 p40. In addition, knockdown of RIP2 reduced phosphorylation of p38 MAPK, ERK and IkappaBalpha, which are known upstream regulators of IL-12 production. Thus, in human DC LPS stimulates a signal cascade that involves the Raf-dependent activation of RIP2 leading to expression of IL-12 p40.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Transdução de Sinais
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Proteínas I-kappa B
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Proteínas Quinases p38 Ativadas por Mitógeno
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Proteína Serina-Treonina Quinase 2 de Interação com Receptor
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Subunidade p40 da Interleucina-12
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
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