Deletion of PPARγ in Alveolar Macrophages Is Associated with a Th-1 Pulmonary Inflammatory Response
Deletion of PPARγ in Alveolar Macrophages Is Associated with a Th-1 Pulmonary Inflammatory Response
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DOI：
10.4049/jimmunol.0803504
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发表时间：
2009-05-01
影响因子：
4.4
通讯作者：
Thomassen, Mary Jane
中科院分区：
文献类型：
--
作者：
Malur, Anagha;Mccoy, Almedia J.;Thomassen, Mary Jane
与其他组织巨噬细胞和血液单核细胞相比，过氧化物酶体增殖物激活受体γ（PPAR γ）在健康肺泡巨噬细胞中以高水平组成型表达。已经显示出PPAR γ配体下调巨噬细胞中IFN-γ刺激的诱导型NO合酶（iNOS）。由于NO是肺中重要的炎症介质，我们假设体内肺泡巨噬细胞PPAR γ的缺失将导致iNOS和其他炎症介质的上调。通过将floxed（+/+）PPAR-gamma小鼠与含有在鼠M溶菌酶启动子控制下的CRE重组酶基因的转基因小鼠（PPARgamma KO）杂交来实现巨噬细胞中PPARgamma的损失。通过支气管肺泡灌洗（BAL）收获肺泡巨噬细胞。与野生型C57 BL 6相比，PPAR γ KO的BAL中淋巴细胞（CD 8：CD 4比值= 2.8）增加; p
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is constitutively expressed at high levels in healthy alveolar macrophages, in contrast to other tissue macrophages and blood monocytes. PPAR gamma ligands have been shown to down-regulate IFN-gamma-stimulated inducible NO synthase (iNOS) in macrophages. Because NO is an important inflammatory mediator in the lung, we hypothesized that deletion of alveolar macrophage PPAR gamma in vivo would result in up-regulation of iNOS and other inflammatory mediators. The loss of PPAR gamma in macrophages was achieved by crossing floxed (+/+) PPAR-gamma mice and a transgenic mouse containing the CRE recombinase gene under the control of the murine M lysozyme promoter (PPAR gamma KO). Alveolar macrophages were harvested by bronchoalveolar lavage (BAL). Lymphocytes (CD8:CD4 ratio = 2.8) were increased in BAL of PPAR gamma KO vs wild-type C57BL6; p