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

IF 2.9 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Michiko Miyazaki, Masafumi Zaitsu, Kinji Honjo, Eiichi Ishii, Yuhei Hamasaki
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引用次数: 17

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.

大环内酯类抗生素抑制人白细胞前列腺素E2合成及前列腺素合成酶mRNA表达。
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合成和人白细胞胞质磷脂酶A2 (cPLA2)、环氧化酶(COX)-1和COX-2 mrna表达的作用。lps刺激的外周多形核白细胞(PMNLs)和单核白细胞(MNLs)中PGE2的产生显著增加。LPS在PMNLs和MNLs中增加了COX-2和cPLA2 mrna的数量,但没有增加COX-1 mrna的数量。克拉霉素、阿奇霉素和地塞米松抑制了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 mRNA的表达。大环内酯类抗生素通过抑制cPLA2、COX-1和COX-2 mRNA表达抑制人白细胞PGE2合成。这些数据提示了大环内酯类抗炎活性的一种机制。
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来源期刊
CiteScore
6.40
自引率
6.70%
发文量
60
审稿时长
13.2 weeks
期刊介绍: The role of lipids, including essential fatty acids and their prostaglandin, leukotriene and other derivatives, is now evident in almost all areas of biomedical science. Cell membrane behaviour and cell signalling in all tissues are highly dependent on the lipid constituents of cells. Prostaglandins, Leukotrienes & Essential Fatty Acids aims to cover all aspects of the roles of lipids in cellular, organ and whole organism function, and places a particular emphasis on human studies. Papers concerning all medical specialties are published. Much of the material is particularly relevant to the development of novel treatments for disease.
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