RIP2 mediates LPS-induced p38 and IκBα signaling including IL-12 p40 expression in human monocyte-derived dendritic cells
✍ Scribed by Nurguel Usluoglu; Jovan Pavlovic; Karin Moelling; Gerald Radziwill
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 230 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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‐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.