Exp Mol Med.  2005 Aug;37(4):323-334.

beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macro phages by suppressing redox-based NF-kappaB activation

• Bai SK
• Lee SJ
• Na HJ
• Ha KS
• Han JA
• Lee H
• Kwon YG
• Chung CK
• Kim YM

Abstract

beta-Carotene has shown antioxidant and antiinflammatory activities; however, its molecular mechanism has not been clearly defined. We examined in vitro and in vivo regulatory function of beta-carotene on the production of nitric oxide (NO) and PGE2 as well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, TNF-alpha, and IL-1beta. beta-Carotene inhibited the expression and production of these inflammatory mediators in both LPSstimulated RAW264.7 cells and primary macrophages in a dose-dependent fashion as well as in LPS-administrated mice. Furthermore, this compound suppressed NF-kappaB activation and iNOS promoter activity in RAW264.7 cells stimulated with LPS. beta-Carotene blocked nuclear translocation of NF-kappaB p65 subunit, which correlated with its inhibitory effect on IkappaBalpha phosphorylation and degradation. This compound directly blocked the intracellular accumulation of reactive oxygen species in RAW264.7 cells stimulated with LPS as both the NADPH oxidase inhibitor diphenylene iodonium and antioxidant pyrrolidine dithiocarbamate did. The inhibition of NADPH oxidase also inhibited NO production, iNOS expression, and iNOS promoter activity. These results suggest that beta-carotene possesses anti-inflammatory activity by functioning as a potential inhibitor for redox-based NF-kappaB activation, probably due to its antioxidant activity.

Keyword

beta-carotene; cytokines; macrophages; nitric oxide; NF-kappaB; reactive oxygen species.

MeSH Terms

Animals
Anti-Inflammatory Agents/*pharmacology
Antioxidants/*pharmacology
Dinoprostone/metabolism
Female
Gene Expression/drug effects
Inflammation Mediators/*metabolism
Lipopolysaccharides/pharmacology
Macrophages/*drug effects
Mice
Mice, Inbred BALB C
NF-kappa B/*antagonists & inhibitors/genetics/metabolism
Nitric Oxide/metabolism
Oxidation-Reduction
Research Support, Non-U.S. Gov't
beta Carotene/*pharmacology