Vitamin D receptor ligands attenuate the inflammatory profile of IL-1β-stimulated human white preadipocytes via modulating the NF-κB and unfolded protein response pathways

Zhu, Jingjing, Bing, Chen and Wilding, John PH ORCID: 0000-0003-2839-8404 (2018) Vitamin D receptor ligands attenuate the inflammatory profile of IL-1β-stimulated human white preadipocytes via modulating the NF-κB and unfolded protein response pathways. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 503 (2). pp. 1049-1056.

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Abstract

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-1β might induce metaflammation in adipose tissue via modulating the NF-κB signaling pathway. In our study, the mRNA and secretion levels of major pro-inflammatory factors including IL (interleukin)-1β, 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-1β could induce adipose tissue metaflammation by enhancing the inflammatory profile of preadipocytes. Moreover, IL-1β could enhance pro-inflammatory gene expression by increasing the phosphorylation or decreasing the methylation of relA (NF-κB p65) of the NF-κB 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-1β-stimulated preadipocytes is significantly attenuated by VDR ligands 1α,25(OH)₂D₃, 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 1α,25(OH)₂D₃, ZK159222 and ZK191785 via increasing the phosphorylation of eIF (eukaryotic translation initiation factor)-2α 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.

Item Type:	Article
Uncontrolled Keywords:	Preadipocyte, IL-1 beta, Inflammatory profile, VDR ligands, reIA, eIF-2 alpha
Depositing User:	Symplectic Admin
Date Deposited:	25 Sep 2018 09:12
Last Modified:	13 Oct 2023 20:15
DOI:	10.1016/j.bbrc.2018.06.115
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3025930