大环内酯类抗生素可抑制人白细胞中前列腺素E2的合成以及前列腺素合成酶的mRNA表达。

Macrolide antibiotics inhibit prostaglandin E2 synthesis and mRNA expression of prostaglandin synthetic enzymes in human leukocytes.

作者信息

Miyazaki Michiko, Zaitsu Masafumi, Honjo Kinji, Ishii Eiichi, Hamasaki Yuhei

机构信息

Department of Pediatrics, Faculty of Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2003 Oct;69(4):229-35. doi: 10.1016/s0952-3278(03)00089-9.

DOI:10.1016/s0952-3278(03)00089-9

PMID:12907132

Abstract

We investigated the action of macrolide antibiotics, which are considered to have anti-inflammatory activity, on lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E2 synthesis and the expression of mRNAs for cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 in human leukocytes. The production of LPS-stimulated PGE2 was significantly increased in peripheral polymorphonuclear leukocytes (PMNLs) and in mononuclear leukocytes (MNLs). Amounts of mRNAs for COX-2 and cPLA2, but not for COX-1, were enhanced by LPS in PMNLs and MNLs. The LPS-enhanced PGE2 synthesis and the expression of cPLA2 and COX-2 mRNAs were inhibited by clarithromycin, azithromycin and dexamethasone in PMNLs and MNLs. The mRNA expression of COX-1 in PMNLs was decreased by clarithromycin and azithromycin. Macrolide antibiotics inhibited PGE2 synthesis in human leukocytes by suppressing cPLA2, COX-1, and COX-2 mRNA expression. These data indicate one mechanism of macrolide anti-inflammatory activity.

摘要

我们研究了被认为具有抗炎活性的大环内酯类抗生素对脂多糖（LPS）刺激的前列腺素（PG）E2合成以及人白细胞中胞质磷脂酶A2（cPLA2）、环氧化酶（COX）-1和COX-2 mRNA表达的作用。LPS刺激的PGE2在外周多形核白细胞（PMNLs）和单核白细胞（MNLs）中的产生显著增加。LPS可增强PMNLs和MNLs中COX-2和cPLA2的mRNA量，但不增强COX-1的mRNA量。克拉霉素、阿奇霉素和地塞米松可抑制PMNLs和MNLs中LPS增强的PGE2合成以及cPLA2和COX-2 mRNA的表达。克拉霉素和阿奇霉素可降低PMNLs中COX-1的mRNA表达。大环内酯类抗生素通过抑制cPLA2、COX-1和COX-2 mRNA表达来抑制人白细胞中PGE2的合成。这些数据表明了大环内酯类抗炎活性的一种机制。