Epidermal-type fatty acid binding protein as a negative regulator of IL-12 production in dendritic cells
Epidermal-type fatty acid binding protein as a negative regulator of IL-12 production in dendritic cells
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DOI：
10.1016/j.bbrc.2006.04.114
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发表时间：
2006-06-23
影响因子：
3.1
通讯作者：
Kondo, Hisatake
中科院分区：
文献类型：
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作者：
Kitanaka, Noriko;Owada, Yuji;Kondo, Hisatake
脂肪酸及其代谢产物可调节树突状细胞（DC）的分化和细胞因子的产生等多种功能，但其作用机制尚不完全清楚。鉴于我们先前发现表皮型脂肪酸结合蛋白（epidermal-type fatty acid binding protein，E-FABP）在FABP家族中仅在脾脏DCs中表达，我们检测E-FABP缺失突变小鼠的表型，以阐明E-FABP在DCs中表达的功能意义。虽然E-FABP-null突变小鼠在DC的群体密度和亚群分布以及脾脏中的显微形态学上没有表现出明显的异常，但与野生型相比，从E-FABP-null脾脏分离的DC在响应于适当的刺激时显示出IL-12 p70（先天免疫应答的关键细胞因子）的产生增强。实时荧光定量PCR结果显示，LPS刺激后，突变型DC中IL-12 p35 mRNA的表达水平明显高于野生型DC，而IL-12 p40 mRNA的表达水平无明显变化。与野生型相比，LPS刺激后，E-FABP缺失突变型DC中检测到p38丝裂原活化蛋白激酶（p38 MAPK）和I κ Bot（IL-12产生的关键分子）的磷酸化形式处于更高水平。总的来说，这表明，E-FABP可能是一种新的负调节IL-12的生产在DC中，这种调节可能是通过其参与p38 MAPK介导的IL-12 p35的转录。(c)2006年爱思唯尔公司All rights reserved.
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 I kappa Bot, 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. (c) 2006 Elsevier Inc. All rights reserved.