Gene interactions and pathways from curated databases and text-mining
Eur J Immunol 2007, PMID: 17578844

RIP2 mediates LPS-induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte-derived dendritic cells.

Usluoglu, Nurguel; Pavlovic, Jovan; Moelling, Karin; Radziwill, Gerald

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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Text Mining Data

p38 → RIP2: " RIP2 mediates LPS induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte derived dendritic cells "

p38 → LPS: " RIP2 mediates LPS induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte derived dendritic cells "

IkappaBalpha → RIP2: " RIP2 mediates LPS induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte derived dendritic cells "

IkappaBalpha → LPS: " RIP2 mediates LPS induced p38 and IkappaBalpha signaling including IL-12 p40 expression in human monocyte derived dendritic cells "

IL-12 → LPS: " IL-12 , the critical factor for the generation of the Th1 type immune response, is produced by dendritic cells ( DC ) upon stimulation with LPS "

IL-12 → LPS: " Different signal pathways mediate LPS induced expression of IL-12 and involve PI3K, MAPK and the transcription factor NF-kappaB "

MAPK — IL-12: " Different signal pathways mediate LPS induced expression of IL-12 and involve PI3K, MAPK and the transcription factor NF-kappaB "

IL-12 — NF-kappaB: " Different signal pathways mediate LPS induced expression of IL-12 and involve PI3K, MAPK and the transcription factor NF-kappaB "

IL-12 — PI3K: " Different signal pathways mediate LPS induced expression of IL-12 and involve PI3K , MAPK and the transcription factor NF-kappaB "

p40 → LPS: " Knockdown of RIP2 by siRNA inhibited LPS dependent expression of IL-12 p40 "

Manually curated Databases

No curated data.