Regulatory effects of estrogen on acute lung inflammation in mice
Regulatory effects of estrogen on acute lung inflammation in mice
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DOI：
10.1152/ajpcell.00467.2004
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发表时间：
2005-04-01
影响因子：
5.5
通讯作者：
Ward, PA
中科院分区：
文献类型：
--
作者：
Speyer, CL;Rancilio, NJ;Ward, PA
雌激素在炎症反应调节中的作用还没有很好的定义。在这项研究中，我们研究了卵巢激素对小鼠肺部急性炎症反应的影响。用细菌脂多糖（LPS）诱导雄性、雌性和去卵巢（OVX）小鼠急性肺损伤。损伤的终点是支气管肺泡灌洗液（BAL）中多形中性粒细胞（PMN）含量、全肺髓过氧化物酶活性和白蛋白渗漏入肺。腹腔内灌注LPS后，雄性和OVX小鼠的所有损伤终点均显著高于卵巢完整的雌性小鼠。所有小鼠的支气管肺泡灌洗液显示趋化因子（巨噬细胞炎性蛋白MIP-2，KC和单核细胞趋化蛋白MCP-1和MCP-3）和TNF-α的水平相似，但在OVX和雄性小鼠中发现IL-1 β水平升高。与卵巢完整的雌性小鼠相比，LPS滴注后，OVX小鼠和雄性小鼠肺匀浆中的血清IL-6和ICAM-1水平也升高。在OVX小鼠中给予雌二醇后，LPS损伤的肺中的白蛋白和PMN含量降低至雌性小鼠中发现的水平，并且对应于降低的IL-1 β、IL-6和ICAM-1水平。这些数据表明，雌激素通过影响血管细胞粘附分子和促炎介质抑制小鼠的肺部炎症反应。
The role of estrogen in the regulation of the inflammatory response is not well defined. In this study, we investigated the effects of ovarian hormones on the acute inflammatory response in mouse lungs. Acute lung injury was induced by intratracheal instillation of bacterial lipopolysaccharide (LPS) in male, female, and ovariectomized (OVX) mice. End points of injury were polymorphonuclear neutrophil (PMN) content in bronchoalveolar lavage (BAL) fluids, myeloperoxidase activity in whole lung, and leak of albumin into the lung. After intratracheal instillation of LPS, all end points of injury were substantially increased in male and OVX mice compared with the female mice with intact ovaries. BAL fluids of all mice showed similar levels of chemokines ( macrophage inflammatory protein MIP-2, KC, and monocyte chemoattractant proteins MCP-1 and MCP-3) and TNF-alpha, but enhanced levels of IL-1 beta were found in OVX and male mice. Serum levels of IL-6 and ICAM-1 levels in lung homogenates from OVX and male mice, compared with those in female mice with intact ovaries, were also enhanced after instillation of LPS. Albumin and PMN content in LPS-injured lungs were reduced to levels found in female mice after administration of estradiol in OVX mice and corresponded to reduced IL-1 beta, IL-6, and ICAM-1 levels. These data suggest that estrogen suppresses lung inflammatory responses in mice through an effect on vascular cell adhesion molecules and proinflammatory mediators.