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

抄録

Reactive oxygen species (ROS) including hydrogen peroxide (H₂O₂) are involved in the pathogenesis of gastric inflammation. Interleukin-8 (IL-8) is a potent mediator of the inflammatory response by activating and recruiting neutrophils to the site of infection. Oxidant-sensitive transcription factor NF-κB regulates the expression of IL-8 in the immune and inflammatory events. Carotenoids (carotenes and oxygenated carotenoids) show antioxidant and anti-inflammatory activities. Low intake of β-carotene leads to high risk of gastric cancer. Oxygenated carotenoid lutein inhibited NF-κB activation in experimental uveitis. The present study aims to investigate whether β-carotene and lutein inhibit H₂O₂-induced activation of NF-κB and expression of IL-8 in gastric epithelial AGS cells. The cells were treated with carotenoids 2 h prior to the treatment of H₂O₂. mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR analyses. IL-8 level in the medium was determined by enzyme-linked immunosorbent assay. NF-κB activation was assessed by electrophoretic mobility shift assay. ROS levels of the cells were detected by confocal microscopic analysis for fluorescent dichlorofluorescein. As a result, H₂O₂ induced the activation of NF-κB and expression of IL-8 in AGS cells time-dependently. β-Carotene and lutein showed inhibitory effects on H₂O₂-induced increase in intracellular ROS levels, activation of NF-κB, and IL-8 expression in AGS cells. In conclusion, supplementation of carotenoids such as β-carotene and lutein may be beneficial for the treatment of oxidative stress-mediated gastric inflammation.