Hamaguchi Katsuhiko, Kuwata Hiroshi, Yoshihara Kumiko, Masuda Seiko, Shimbara Satoko, Oh-ishi Sachiko, Murakami Makoto, Kudo Ichiro
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Tokyo 142-8555, Shinagawa, Japan.
Biochim Biophys Acta. 2003 Nov 30;1635(1):37-47. doi: 10.1016/j.bbalip.2003.10.004.
Although the expression of the prototypic secretory phospholipase A(2) (sPLA(2)), group IIA (sPLA(2)-IIA), is known to be up-regulated during inflammation, it remains uncertain if other sPLA(2) enzymes display similar or distinct profiles of induction under pathological conditions. In this study, we investigated the expression of several sPLA(2)s in rodent inflammation models. In lipopolysaccharide (LPS)-treated mice, the expression of sPLA(2)-V, and to a lesser extent that of sPLA(2)-IID, -IIE, and -IIF, were increased, whereas that of sPLA(2)-X was rather constant, in distinct tissues. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema, in which the expression of sPLA(2)-IID, -IIF and -V was increased, was significantly reduced by YM-26734, a competitive sPLA(2)-IIA inhibitor that turned out to inhibit sPLA(2)-IID, -IIE, -V and -X as well. In contrast, sPLA(2)-IIA was dominant in carageenin-induced pleurisy in rats, where the accumulation of exudate fluids and leukocytes was significantly ameliorated by YM-26734. These results indicate that distinct sPLA(2)s can participate in inflammatory diseases according to tissues, animal species, and types of inflammation.
虽然已知原型分泌型磷脂酶A2(sPLA2),即IIA型(sPLA2-IIA)在炎症过程中表达上调,但在病理条件下其他sPLA2酶是否显示出相似或不同的诱导模式仍不确定。在本研究中,我们调查了几种sPLA2在啮齿动物炎症模型中的表达。在脂多糖(LPS)处理的小鼠中,sPLA2-V以及程度较轻的sPLA2-II D、-IIE和-IIF在不同组织中的表达增加,而sPLA2-X的表达相当恒定。12-O-十四烷酰佛波醇-13-乙酸酯(TPA)诱导的小鼠耳部水肿中,sPLA2-II D、-IIF和-V的表达增加,而YM-26734(一种竞争性sPLA2-IIA抑制剂,结果证明也能抑制sPLA2-II D、-IIE、-V和-X)可显著减轻水肿。相比之下,sPLA2-IIA在角叉菜胶诱导的大鼠胸膜炎中占主导地位,YM-26734可显著改善大鼠胸膜炎中渗出液和白细胞的积聚。这些结果表明,不同的sPLA2可根据组织、动物物种和炎症类型参与炎症性疾病。