College of Medicine, Florida Atlantic University, 777 Glades Rd., Boca Raton, FL 33431-0991, USA.
Inflammation. 2012 Oct;35(5):1685-95. doi: 10.1007/s10753-012-9486-x.
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 E(2) release, unlike COX-2 that is active in M1 activation in vitro by BCG. In this study, we determined the role of PPARγ for BCG-induced M1 activation in vivo and in 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 treated in vitro with 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.
初步研究表明，BCG 经鼻腔给药会诱导肺泡巨噬细胞（M∅）的 M1 激活，增加 TNF-α 的产生和环氧化酶-2（COX-2）的表达，但会降低固有过氧化物酶体增殖物激活受体 γ（PPARγ）的表达。然而，与 BCG 在体外诱导的 M1 激活中具有活性的 COX-2 不同，COX-2 对于前列腺素 E（2）的释放没有催化活性。在这项研究中，我们确定了 PPARγ 在体内和体外 BCG 诱导的 M1 激活中的作用。我们发现，在经鼻给予 BCG 之前，用 PPARγ 拮抗剂 GW9662 处理小鼠，部分恢复了 PPARγ 的表达，并降低了 TNF-α 的产生和 COX-2 的表达。但 COX-2 仍然没有活性。当用 GW9662/BCG 处理体外肺泡 M∅ 时，也观察到 TNF-α 和 COX-2 的减少作用，但 COX-2 仍然是有活性的。我们的结果表明，PPARγ 上调了肺泡 M∅ 的 M1 激活，但在分枝杆菌性肺部炎症中，无活性 COX-2 的形成不依赖于 PPARγ。
