Role of PPARγ in COX-2 activation in mycobacterial pulmonary inflammation.
Role of PPARγ in COX-2 activation in mycobacterial pulmonary inflammation.
复制标题
PPARγ 在分枝杆菌肺部炎症中 COX-2 激活中的作用。
DOI：
10.1007/s10753-012-9486-x
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发表时间：
2012
期刊：
影响因子：
5.1
通讯作者：
Shibata,Yoshimi
中科院分区：
文献类型：
--
作者：
Kogiso,Mari;Shinohara,Tsutomu;Dorey,CKathleen;Shibata,Yoshimi
初步研究表明，鼻内（i.n.）小鼠给予BCG诱导肺泡巨噬细胞（M β）M1活化，增加TNF-α产生和环氧合酶-2（考克斯-2）表达，但降低组成型过氧化物酶体增殖物激活受体γ（PPARγ）表达。然而，考克斯-2对前列腺素E2的释放无催化活性，而考克斯-2在BCG体外激活M1中有活性。在本研究中，我们在体内和体外确定了PPARγ在BCG诱导的M1激活中的作用。我们发现，在i.n. BCG部分恢复了PPARγ表达，降低了TNF-α的产生和考克斯-2的表达。但考克斯-2仍无活性。体外培养的肺泡巨噬细胞经GW 9662/BCG处理后，TNF-α和考克斯-2活性明显降低，但考克斯-2仍有活性。我们的研究结果表明，在分枝杆菌肺炎中，PPARγ上调肺泡巨噬细胞M1的活化，但无活性的考克斯-2的形成不依赖于PPARγ。
Preliminary studies show that intranasal (i.n.) administration of BCG in mice induces M1 activation of alveolar macrophages (M∅) that increase TNF-α production and cyclooxygenase-2 (COX-2) expression but reduce constitutive peroxisome proliferator-activated receptor gamma (PPARγ) expression. However, COX-2 is catalytically inactive for prostaglandin E2release, unlike COX-2 that is active in M1 activationin vitroby BCG. In this study, we determined the role of PPARγ for BCG-induced M1 activationin vivoandin vitro. We found that treatment of mice with GW9662, a PPARγ antagonist, prior to i.n. BCG, partially restored PPARγ expression, and decreased TNF-α production and COX-2 expression. But COX-2 was still inactive. The decreased effects on TNF-α and COX-2 were also observed when alveolar M∅ were treatedin vitrowith GW9662/BCG, but COX-2 was still active. Our results indicate that PPARγ upregulates M1 activation of alveolar M∅, but inactive COX-2 formation is independent of PPARγ in mycobacterial pulmonary inflammation.