| Autor: |
Usluoglu, Nurguel, Pavlovic, Jovan, Moelling, Karin, Radziwill, Gerald |
| Zdroj: |
European Journal of Immunology; Aug2007, Vol. 37 Issue 8, p2317-2325, 9p |
| Abstrakt: |
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-κB. 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 IκBα, 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text