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

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

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

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

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

Authors

Michiko Miyazaki¹, Masafumi Zaitsu, Kinji Honjo, Eiichi Ishii, Yuhei Hamasaki

Affiliation

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

PMID: 12907132
DOI: 10.1016/s0952-3278(03)00089-9

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Cyclooxygenase 1
Cyclooxygenase 2
Dinoprostone / antagonists & inhibitors*
Dinoprostone / biosynthesis
Dinoprostone / genetics
Enzyme Inhibitors / pharmacology
Humans
Isoenzymes / antagonists & inhibitors
Leukocytes / drug effects*
Leukocytes / metabolism
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / metabolism
Lipopolysaccharides
Macrolides / pharmacology*
Membrane Proteins
Neutrophils / drug effects
Neutrophils / metabolism
Phospholipases A / antagonists & inhibitors
Phospholipases A2
Prostaglandin-Endoperoxide Synthases
RNA, Messenger / antagonists & inhibitors*
RNA, Messenger / biosynthesis

Substances

Anti-Bacterial Agents
Enzyme Inhibitors
Isoenzymes
Lipopolysaccharides
Macrolides
Membrane Proteins
RNA, Messenger
Cyclooxygenase 1
Cyclooxygenase 2
PTGS1 protein, human
PTGS2 protein, human
Prostaglandin-Endoperoxide Synthases
Phospholipases A
Phospholipases A2
Dinoprostone