Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages

• Published in: Cellular signalling Vol. 15; no. 3; pp. 299 - 306
• Main Authors: Kim, Chu-Sook, Kawada, Teruo, Kim, Byung-Sam, Han, In-Seob, Choe, Suck-Young, Kurata, Tadao, Yu, Rina
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.03.2003
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Capsaicin; Capsaicin - pharmacology; Capsazepine; COX-2; Cyclooxygenase 2; Dinoprostone - metabolism; Enzyme Activation - drug effects; Gene Expression Regulation, Enzymologic; I-kappa B Proteins - metabolism; IkB-a; Inflammation; iNOS; Isoenzymes - genetics; Isoenzymes - metabolism; Lipopolysaccharides - pharmacology; Macrophage; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred BALB C; Nitric Oxide - metabolism; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; PGE2; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Receptors, Drug - genetics; Receptors, Drug - metabolism; RNA, Messenger - analysis; TRPV Cation Channels; PGE2; IkB-a; COX-2; Capsaicin; NF-kB; iNOS; Inflammation; Capsazepine; LPS; Macrophage
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/S0898-6568(02)00086-4

Capsaicin, a major ingredient of hot pepper, was considered to exhibit an anti-inflammatory property. In order to clarify the signalling mechanism underlying the anti-inflammatory action of capsaicin, we investigated the effect of capsaicin on the production of inflammatory molecules in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. The level of PGE2 was measured by EIA. The expression levels of COX-2, iNOS, IkB-a, and vanilloid receptor-1 (VR-1) were determined at the protein and mRNA levels. Significant inhibition of the production of LPS-induced PGE2 by capsaicin was observed in a dose-dependent manner. Capsaicin did not affect the COX-2 expression at either the protein or mRNA level, but inhibited the enzyme activity of COX-2 and the expression of the iNOS protein. Capsaicin completely blocked LPS-induced disappearance of IkB-a and therefore inactivated NF-kB. The inhibitory action of capsaicin on PGE2 production was not abolished by capsazepine, a specific antagonist to VR-1. A high expression level of the VR-1 like protein (VRL-1) was observed in peritoneal macrophages, while the expression of VR-1 was not detected. These findings suggest that the anti-inflammatory action of capsaicin may occur through a novel mechanism, not by a VR-1 receptor-mediated one. Both capsaicin and capsazepine may be a promising drug candidates for ameliorating inflammatory diseases and cancer.