PMID- 16684508 OWN - NLM STAT- MEDLINE DCOM- 20060711 LR - 20061115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 345 IP - 1 DP - 2006 Jun 23 TI - Epidermal-type fatty acid binding protein as a negative regulator of IL-12 production in dendritic cells. PG - 459-66 AB - Fatty acids and their metabolites have recently been shown to modulate various functions of dendritic cells (DCs) including their differentiation and cytokine production, although the mechanisms underlying their cellular functions are not fully understood. In view of our previous finding that epidermal-type fatty acid binding protein (E-FABP) was exclusively expressed in splenic DCs among FABP family, we examined the phenotype of E-FABP-null mutant mice in order to elucidate the functional significance of E-FABP expression in DCs. Although E-FABP-null mutant mice showed no apparent abnormalities in the population density and subset distribution of DCs as well as the microscopic morphology in the spleen, DCs isolated from E-FABP-null spleen showed enhanced production of IL-12p70, a key cytokine for innate immune responses, in response to appropriate stimuli as compared with wild-type. In real-time PCR, the expression level of IL-12p35 mRNA after LPS stimuli was much higher in mutant DCs when compared with wild-type, while no apparent change of IL-12p40 mRNA level was detected. Phosphorylated forms of p38 mitogen-activated protein kinase (p38MAPK) and IkappaB-alpha, molecules critical for IL-12 production, were detected at higher levels in E-FABP-null-mutant DCs after LPS stimuli when compared with wild-type counterparts. Collectively, it is suggested that E-FABP may be a novel negative regulator of IL-12 production in DCs, and this regulation may be exerted via its involvement in the p38MAPK-mediated transcription of IL-12p35. FAU - Kitanaka, Noriko AU - Kitanaka N AD - Department of Histology, Graduate School of Medicine, Tohoku University, Japan. FAU - Owada, Yuji AU - Owada Y FAU - Okuyama, Ryuhei AU - Okuyama R FAU - Sakagami, Hiroyuki AU - Sakagami H FAU - Nourani, Mohammad Reza AU - Nourani MR FAU - Aiba, Setsuya AU - Aiba S FAU - Furukawa, Hiroshi AU - Furukawa H FAU - Watanabe, Makoto AU - Watanabe M FAU - Ono, Masao AU - Ono M FAU - Ohteki, Toshiaki AU - Ohteki T FAU - Kondo, Hisatake AU - Kondo H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060502 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (FABP5 protein, human) RN - 0 (Fatty Acid-Binding Proteins) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Cells, Cultured MH - Dendritic Cells/*metabolism MH - Down-Regulation/physiology MH - Fatty Acid-Binding Proteins/genetics/*metabolism MH - Interleukin-12/*metabolism MH - Mice MH - Mice, Inbred C57BL EDAT- 2006/05/11 09:00 MHDA- 2006/07/13 09:00 CRDT- 2006/05/11 09:00 PHST- 2006/04/08 00:00 [received] PHST- 2006/04/17 00:00 [accepted] PHST- 2006/05/11 09:00 [pubmed] PHST- 2006/07/13 09:00 [medline] PHST- 2006/05/11 09:00 [entrez] AID - S0006-291X(06)00891-6 [pii] AID - 10.1016/j.bbrc.2006.04.114 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2006 Jun 23;345(1):459-66. doi: 10.1016/j.bbrc.2006.04.114. Epub 2006 May 2.