Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages.
We have previously shown that ivermectin inhibits LPS-induced production of inflammatory cytokines. In the present study, we investigated the effect of ivermectin on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Ivermectin inhibited LPS-induced NO and PGE(2) production. Consistent with these observations, the protein and mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes were inhibited by ivermectin in a concentration-dependent manner. Furthermore, the phosphorylation of p38, ERK1/2, and JNK in LPS-stimulated RAW 264.7 cells was suppressed by ivermectin in a dose-dependent manner. These results suggest that ivermectin suppresses NO and PGE(2) production, as well as iNOS and COX-2 expression, by inhibiting phosphorylation of mitogen-activated protein kinases (MAPK) (p38, ERK1/2, and JNK) in LPS-stimulated RAW 264.7 cells.
Zhang
Xuemei
X
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
Song
Yu
Y
Xiong
Huanzhang
H
Ci
Xinxin
X
Li
Hongyu
H
Yu
Lu
L
Zhang
Lei
L
Deng
Xuming
X
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007559:Ivermectin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007559:Ivermectin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone