Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation
Proinflammatory role of glucocorticoid-induced TNF receptor-related gene in acute lung inflammation
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DOI：
10.4049/jimmunol.177.1.631
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发表时间：
2006-07-01
影响因子：
4.4
通讯作者：
Riccardi, Carlo
中科院分区：
文献类型：
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作者：
Cuzzocrea, Salvatore;Nocentini, Giuseppe;Riccardi, Carlo
糖皮质激素诱导的肿瘤坏死因子受体相关基因（GITR）参与免疫/炎症反应。由于GITR表达已被描述在T淋巴细胞以外的细胞中，我们研究了它是否也调节急性炎症反应。使用GITR缺陷（GITR（-/-））小鼠，我们通过研究角叉菜胶注射后2-8小时的几种促炎标志物来分析GITR在角叉菜胶诱导的肺部炎症（胸膜炎）发展中的作用。当与GITR（+/+）相比时，GITR（-/-）小鼠表现出含有较低数量的白细胞的浑浊渗出物的产生减少。这与胸膜渗出物和/或肺中炎性标志物（包括TNF-α、IL-1 β、髓过氧化物酶、诱导型NO合酶和环氧合酶2）的减少相关。此外，内皮细胞表达较低水平的粘附分子。在GITR（+/+）小鼠的肺中，GITR配体表达在胸膜炎期间不受调节，而GITR的表达增加，这是GITR表达细胞的浸润增加以及巨噬细胞和内皮细胞中GITR上调的结果。最后，与单独的角叉菜胶治疗相比，用角叉菜胶和Fc-GITR融合蛋白共同治疗GITR（+/+）小鼠减少了炎性细胞（胸膜巨噬细胞和肺嗜中性粒细胞）的数量，证实GITR在胸膜炎的调节中起作用。
Glucocorticoid-induced TNFR-related gene (GITR) participates in the immune/inflammatory response. Because GITR expression has been described in cells other than T lymphocytes, we investigated whether it also modulates acute inflammatory response. Using GITR-deficient (GITR(-/-)) mice, we analyzed the role of GITR in the development of carrageenan-induced lung inflammation (pleurisy) by studying several proinflammatory markers 2-8 h after carrageenan injection. When compared with GITR(+/+), GITR(-/-) mice exhibited decreased production of turbid exudate containing a lower number of leukocytes. This was correlated with the reduction of inflammatory markers (including TNF-alpha, IL-1 beta, myeloperoxidase, inducible NO synthase, and cyclooxygenase 2) in the pleural exudate and/or in the lung. Moreover, endothelial cells expressed lower levels of adhesion molecules. In lungs of GITR(+/+) mice, GITR ligand expression was not modulated during pleurisy, while that of GITR increased, as a consequence of increased infiltration by GITR-expressing cells and of GITR up-regulation in macrophages and endothelial cells. Finally, cotreatment of GITR(+/+) mice with carrageenan and Fc-GITR fusion protein decreased the number of inflammatory cells (pleural macrophages and lung neutrophils) as compared with carrageenan treatment alone, confirming that GITR plays a role in the modulation of pleurisy.