Prostaglandin Receptors EP2, EP3, and IP Mediate Exudate Formation in Carrageenin-Induced Mouse Pleurisy
Prostaglandin Receptors EP2, EP3, and IP Mediate Exudate Formation in Carrageenin-Induced Mouse Pleurisy
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DOI：
10.1124/jpet.104.071548
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发表时间：
2004-12
影响因子：
3.5
通讯作者：
Koh-ichi Yuhki;A. Ueno;H. Naraba;Fumiaki Kojima;F. Ushikubi;S. Narumiya;S. Oh‐ishi
中科院分区：
文献类型：
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作者：
Koh-ichi Yuhki;A. Ueno;H. Naraba;Fumiaki Kojima;F. Ushikubi;S. Narumiya;S. Oh‐ishi
已经广泛研究了洋地黄素（PGs）作为炎症介质的作用，并且已经报道了在炎症部位产生PGI 2和PGE 2。然而，它还没有澄清哪种类型的PG受体在炎症渗出中具有主要作用。为了研究PG受体在炎症渗出中的体内作用，我们通过胸膜内注射角叉菜胶在PG受体（IP、EP 1、EP 2、EP 3或EP 4）敲除小鼠中诱导胸膜炎。在1至5小时，但不是在24小时，在野生型（WT）小鼠的胸膜渗出液的积累，显着衰减的预处理与吲哚美辛，表明前列腺素是负责渗出液形成在胸膜炎的早期阶段。与WT小鼠相比，IP、EP 2或EP 3敲除小鼠1 - 5 h的胸膜渗出显著减少，但EP 1和EP 4敲除小鼠的胸膜渗出未显著减少。在渗出液中，6-keto-PGF 1 α和PGE 2为主要的前列腺素，均在3 h达到峰值。此外，激肽酶抑制剂Captopril可促进渗出液的形成，增加6-keto-PGF_（1 α）和PGE_（2）的含量，而缓激肽B_2受体拮抗剂可抑制渗出液的形成，这表明缓激肽参与了上述现象。与此相反，白细胞迁移到胸膜腔不受吲哚美辛治疗，也不受这些受体缺陷。这些结果表明，在角叉菜胶诱导的小鼠胸膜炎中，EP 2和EP 3沿着IP参与胸膜渗出物形成，但不参与白细胞迁移。
The roles of prostaglandins (PGs) as mediators of inflammation have been extensively studied, and production of PGI2 and PGE2 at inflammatory sites has been reported. However, it has not yet been clarified which type of PG receptors has a major role in inflammatory exudation. To examine in vivo role of PG receptors in inflammatory exudation, we induced pleurisy in PG receptors (IP, EP1, EP2, EP3, or EP4) knockout mice by intrapleural injection of carrageenin. Pleural exudate accumulation in wild-type (WT) mice at 1 to 5 h, but not at 24 h, was significantly attenuated by the pretreatment with indomethacin, indicating that PGs are responsible for exudate formation at the early phase of pleurisy. Pleural exudation at 1 to 5 h in IP, EP2, or EP3 knockout mice, but not in EP1 and EP4 knockout, was significantly reduced compared with in WT mice. In the exudates, 6-keto-PGF1α and PGE2 were detected as the major PGs, each with its peak concentration at 3 h. In addition, involvement of bradykinin in the phenomenon was suggested by the fact that captopril, a kininase inhibitor, enhanced the exudate formation and increased the amount of 6-keto-PGF1α and PGE2 and that a bradykinin B2-receptor antagonist inhibited the exudate formation. In contrast, leukocyte migration into pleural cavity was not influenced by indomethacin-treatment nor by these receptor deficiencies. These results demonstrate participation of EP2 and EP3 along with IP in pleural exudate formation but not in leukocyte migration in carrageenin-induced mouse pleurisy.