COX-2-derived prostacyclin protects against bleomycin-induced pulmonary fibrosis
COX-2-derived prostacyclin protects against bleomycin-induced pulmonary fibrosis
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DOI：
10.1152/ajplung.00492.2005
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发表时间：
2006-08-01
影响因子：
4.9
通讯作者：
Koller, Beverly H.
中科院分区：
文献类型：
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作者：
Lovgren, Alysia Kern;Jania, Leigh A.;Koller, Beverly H.
前列环素是环氧合酶(COX)代谢花生四烯酸所产生的多种脂质介质之一。这种前列腺素是一种有效的血小板聚集抑制物，它由内皮细胞产生并在血管系统中发挥保护作用已得到充分证实。相比之下，人们对这种前列腺素在其他疾病过程中的作用知之甚少。我们在这里表明，COX-2依赖的前列环素的产生在纤维化肺疾病的发展中起着重要的作用，限制了纤维化的发展和随后的肺力学改变。与之形成鲜明对比的是，前列腺素E-2合成的缺失和通过G(S)偶联的EP2和EP4受体传递的信号对疾病的发展没有影响。这些发现表明前列环素类似物对博莱霉素诱导的COX-2(-/-)小鼠肺纤维化有保护作用。如果观察到这种保护作用，那么这些药物作为人类肺纤维化的一种新的治疗方法的研究可能是合理的。
Prostacyclin is one of a number of lipid mediators elaborated from the metabolism of arachidonic acid by the cyclooxygenase ( COX) enzymes. This prostanoid is a potent inhibitor of platelet aggregation, and its production by endothelial cells and protective role in the vasculature are well established. In contrast, much less is known regarding the function of this prostanoid in other disease processes. We show here that COX-2-dependent production of prostacyclin plays an important role in the development of fibrotic lung disease, limiting both the development of fibrosis and the consequential alterations in lung mechanics. In stark contrast, loss of prostaglandin E-2 synthesis and signaling through the G(s)-coupled EP2 and EP4 receptors had no effect on the development of disease. These findings suggest that prostacyclin analogs will protect against bleomycin-induced pulmonary fibrosis in COX-2(-/-) mice. If such protection is observed, investigation of these agents as a novel therapeutic approach to pulmonary fibrosis in humans may be warranted.