Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 9, Issue 3, Pages 354-359Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2008.12.016
Keywords
Ivermectin; NO; PGE(2); iNOS; COX-2; MAPK
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Funding
- National Natural Science Foundation of China [30671586]
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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, ERK7/2, and JNK) in LPS-stimulated RAW 264.7 cells. (C) 2009 Elsevier B.V. All rights reserved.
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