β-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-κB activation

Abstract

Abstractβ-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 β-carotene on the production of nitric oxide (NO) and PGE2 as well as expression of inducible NO synthase (iNOS), cyclooxygenase-2, TNF-α, and IL-1β. β-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-κB activation and iNOS promoter activity in RAW264.7 cells stimulated with LPS. β-Carotene blocked nuclear translocation of NF-κB p65 subunit, which correlated with its inhibitory effect on IκBα 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 β-carotene possesses anti-inflammatory activity by functioning as a potential inhibitor for redox-based NF-κB activation, probably due to its antioxidant activity.

Evaluation of Anti-Inflammatory and Anti-Proliferative Effect of Hydroxy-, Keto-, and Epoxy-Carotenoids in RAW 264.7 and HL-60 Cells

“…Further the key biomarker of inflammation, NF-κB p65 inhibits the expression by 3.5 and 4.7 folds in FUCO than AST and LUT. These results are well supported by earlier report with inhibition of NO production, prostaglandins, and related expression of inflammatory genes by suppressing the activation of transcription factor NF-κB p65 by hydrocarbon carotenoid β-carotene [34].…”

“…FUCO treatment attenuates the productions of NO and PGE 2 by inhibiting inducible NO synthase (iNOS) and cyclooxigenase-2 (COX-2) expressions. The anti-inflammatory activities of selected oxygenated carotenoids may be due to the suppression of NF-κB as similar to previous observation [5,34]. NF-κB plays a decisive role in the transcriptional regulation of a wide range of genes that are involved in regulation of inflammatory and immunity.…”

Eryngium foetidum Suppresses Inflammatory Mediators Produced by Macrophages

“…The E. foetidum leaf extract contains kaempferol, chlorogenic acid, caffeic acid, lutein, and β-carotene. All components have been previously reported to have anti-inflammatory activities, and some also have antioxidant activities (Ching et al, 2002;Lee et al, 2004;Shin et al, 2004;Bai et al, 2005;Kowalski et al, 2005;dos Santos et al, 2006;Hamalainen et al, 2007;Chao et al, 2009;Shan et al, 2009;Zhang et al, 2010). Several bioactive compounds in E. foetidum leaves were recently reported (Paul et al, 2010) to play a role in anti-inflammatory and antioxidant activities.…”

β-Carotene and Lutein Inhibit Hydrogen Peroxide-Induced Activation of NF-κB and IL-8 Expression in Gastric Epithelial AGS Cells

“…␤-Carotene inhibited H. pylori-induced increase in ROS level, the activation of mitogen-activated protein kinases (p38, the c-Jun NH2-terminal protein kinases, the extracellular signal-regulated kinases), NF-B, and AP-1 and the expression of iNOS and COX-2 in AGS cells (31). ␤-Carotene inhibited inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing NF-B activation (27).…”

“…␤ -Carotene induces cell growth inhibition and apoptosis in human breast cancer and colon cancer ( 23 , 24 ). Moreover, ␤ -carotene inhibits inflammatory gene expression by suppressing the activation of NF-B (25)(26)(27). Lutein is a member of the oxygenated carotenoids found particularly in dark-green leafy vegetables.…”