Yang Jin, Li Ang, Yang Qian, Li Xu
Department of Medical Oncology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2006 May;22(3):296-8.
To investigate the role of peroxisome proliferator-activated receptor a (PPARa) in the function and development of murine immune system.
Wild-type and PPARa-null C57B/6 mice were sacrificed after 7-day dietary treatment of with peroxisome proliferator (PP). The changes in the weight of the thymus and spleen and cell numbers from the thymus and spleen were observed. The alterations of the cell phenotypes in bone marrow, thymus and spleen were determined by immunofluorescent staining using anti-mouse CD3, CD4, CD8a, CD19, IgM or CD45R/220 mAb through FACS analysis. The proliferation of T or B cells in response to ConA or LPS, respectively, was analyzed by 3H-TdR labeling. The PPARa mRNA expression in the bone marrow, thymus and spleen was examined by RT-PCR.
PP treatment caused significant decreases in the weight and cell numbers of thymus and spleen and proliferative responsiveness of lymphocytes to ConA and LPS in wild-type mice, whereas these effects were significantly weaker in PPARalpha-null mice. The significant decreases of the CD4+ CD8+ population existed in the thymus and pro/pre-B cells and total B220+ cells in the bone marrow of wild-type mice with PP treatment, but not in PPARa-null mice. Interestingly, PPARalpha expression was detected in mouse thymus and spleen, rather than bone marrow.
PPARalpha plays a major role in the PP-induced immunomodulation, indirectly affecting the development of T and B cells.
研究过氧化物酶体增殖物激活受体α（PPARα）在小鼠免疫系统功能及发育中的作用。
用过氧化物酶体增殖物（PP）对野生型和PPARα基因敲除的C57B/6小鼠进行7天的饮食处理后处死。观察胸腺和脾脏重量及胸腺和脾脏细胞数量的变化。通过流式细胞术分析，使用抗小鼠CD3、CD4、CD8α、CD19、IgM或CD45R/B220单克隆抗体进行免疫荧光染色，确定骨髓、胸腺和脾脏中细胞表型的改变。分别用3H-TdR标记分析T细胞或B细胞对刀豆蛋白A（ConA）或脂多糖（LPS）的增殖反应。通过逆转录聚合酶链反应（RT-PCR）检测骨髓、胸腺和脾脏中PPARα mRNA的表达。
PP处理导致野生型小鼠胸腺和脾脏重量、细胞数量以及淋巴细胞对ConA和LPS的增殖反应显著降低，而在PPARα基因敲除小鼠中这些作用明显较弱。PP处理的野生型小鼠胸腺中CD4+CD8+群体以及骨髓中的前B细胞/前B细胞和总B220+细胞显著减少，但在PPARα基因敲除小鼠中未出现这种情况。有趣的是，在小鼠胸腺和脾脏中检测到PPARα表达，而在骨髓中未检测到。
PPARα在PP诱导的免疫调节中起主要作用，间接影响T细胞和B细胞的发育。
