首页|High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1β production in monocytes:the modulatory effects of EGCG
High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1β production in monocytes:the modulatory effects of EGCG
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Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetes-relevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1β release.
Epigallocatechin gallate(EGCG)InflammasomeNuclear factor erythroid 2-related factor 2(Nrf2)Receptor for advanced glycation end products(RAGE)Soluble RAGE(sRAGE)
Chi-Hao Wu、Yin-Hsuan Chang、Chin-Lin Hsu、Sheng-Yi Chen、Gow-Chin Yen
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Graduate Programs of Nutrition Science,School of Life Science,Taiwan Normal University,Taipei 106209,Taiwan,China
Department of Food Science and Biotechnology,Chung Hsing University,Taichung 40227,Taiwan,China
School of Nutrition,Chung Shan Medical University,Taichung 40201,Taiwan,China
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