Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages |
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| Affiliation: | 1. Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People''s Republic of China;2. Department of Animal Medicine, Agricultural College of Yanbian University, Longjing, Jilin 133400, People''s Republic of China;1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt;2. Department of Pharmacology, Toxicology and Biochemistry, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt;3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Egypt;4. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt;5. Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Egypt;6. Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Egypt;7. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt;8. Pharmaceutical Factory, Faculty of Pharmacy, Future University in Egypt, Cairo, Egypt;1. Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong;2. Shenzhen Institute of Integrative Medicine, Shenzhen Second People׳s Hospital, Shenzhen, China;1. School of Health Sciences Jenderal Achmad Yani Cimahi, Jl. Terusan Jenderal Sudirman, Cimahi 40533, West Java, Indonesia;2. Department of Health Analyst, Health Sciences Polytechnic Bandung, Jl. Prof. Eyckman No.24, Bandung 40161, West Java, Indonesia;3. Biomolecular and Biomedical Research Center, Aretha Medika Utama, Jl. Babakan Jeruk 2 No. 9, Bandung 40163, West Java, Indonesia;4. Medical Research Center, Faculty of Medicine, Maranatha Christian University, Jl. Prof drg. Suria Sumantri No.65, Bandung 40164, West Java, Indonesia |
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| Abstract: | 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 E2 (PGE2) production in RAW 264.7 macrophages. Ivermectin inhibited LPS-induced NO and PGE2 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 PGE2 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. |
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