화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.503, No.2, 1049-1056, 2018
Vitamin D receptor ligands attenuate the inflammatory profile of IL-1 beta-stimulated human white preadipocytes via modulating the NF-kappa B and unfolded protein response pathways
Metaflammation in adipose tissue, which is characterized by increased local gene expression and secretion of pro-inflammatory factors, may contribute to the increased risk of metabolic complications in obesity. It has been suggested that IL-1 beta might induce metaflammation in adipose tissue via modulating the NF-kappa B signaling pathway. In our study, the mRNA and secretion levels of major pro-inflammatory factors including IL (interleukin)-1 beta, IL-6, IL-8, MCP (monocyte chemoattractant protein)-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were measured as indicators of the inflammatory profile. We herein showed that IL-1 beta could induce adipose tissue metaflammation by enhancing the inflammatory profile of preadipocytes. Moreover, IL-1 beta could enhance pro-inflammatory gene expression by increasing the phosphorylation or decreasing the methylation of relA (NF-kappa B p65) of the NF-kappa B signaling pathway. VDR (vitamin D receptor) ligands have been shown to have anti-inflammatory properties in adipocytes. Likewise, our study demonstrated that the inflammatory profile of IL-1 beta-stimulated preadipocytes is significantly attenuated by VDR ligands 1 alpha,25(OH)(2)D-3, ZK159222 and ZK191785. Importantly, we showed that ZK159222 and ZK191785 could inhibit pro-inflammatory gene expression by decreasing the phosphorylation or increasing the methylation of relA. Furthermore, pro-inflammatory secretion could be reduced by 1 alpha,25(OH)(2)D-3, ZK159222 and ZK191785 via increasing the phosphorylation of eIF (eukaryotic translation initiation factor)-2 alpha of the UPR (unfolded protein response) pathway. These observations suggest that the VDR ligands may be considered potential anti-inflammatory treatments for obesity associated metabolic complications. (C) 2018 Elsevier Inc. All rights reserved.