1,25(OH)(2)D-3 attenuates IL-6 and IL-1-mediated inflammatory responses in macrophage conditioned medium-stimulated human white preadipocytes by modulating p44/42 MAPK and NF-B signaling pathways

Zhu, Jingjing, Bing, Chen and Wilding, John PH ORCID: 0000-0003-2839-8404 (2019) 1,25(OH)(2)D-3 attenuates IL-6 and IL-1-mediated inflammatory responses in macrophage conditioned medium-stimulated human white preadipocytes by modulating p44/42 MAPK and NF-B signaling pathways. DIABETOLOGY & METABOLIC SYNDROME, 11 (1). 9-.

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1α,25(OH)2D3 attenuates IL-6 and IL-1β-mediated inflammatory responses in macrophage conditioned medium-stimulated human white preadipocytes by modulating p44/42 MAPK and NF-κB signaling pathways.pdf - Published version
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Official URL: http://dx.doi.org/10.1186/s13098-019-0405-2

Abstract

<h4>Background</h4>Metabolic syndrome is characterized by macrophage infiltration and inflammatory responses-metaflammation in adipose tissue. IL-6 and IL-1β could mediate the inflammatory responses in macrophage stimulated-preadipocytes by modulating MAPK and NF-κB pathways. To test this hypothesis we used antibodies to block IL-6 and IL-1β action in macrophage conditioned medium (MacCM)-stimulated human white preadipocytes. Moreover, as interventions that prevent this could potentially be used to treat or prevent metabolic syndrome, and 1α,25(OH)<sub>2</sub>D<sub>3</sub> has previously been reported to exert an anti-inflammatory action on macrophage-stimulated adipocytes, in this study we also investigated whether 1α,25(OH)<sub>2</sub>D<sub>3</sub> could attenuate inflammatory responses in MacCM-stimulated preadipocytes, and explored the potential anti-inflammatory mechanisms.<h4>Methods</h4>Human white preadipocytes were cultured with 25% MacCM for 24 h to elicit inflammatory responses. This was confirmed by measuring the concentrations and mRNA levels of major pro-inflammatory factors [IL-1β, IL-6, IL-8, monocyte chemoattractant protein (MCP)-1 and regulated on activation, normal T cell expressed and secreted (RANTES)] by ELISA and qPCR, respectively. IL-6 and IL-1β actions were blocked using IL-6 antibody (300 ng/ml) and IL-1β antibody (15 μg/ml), respectively. Potential anti-inflammatory effects of 1α,25(OH)<sub>2</sub>D<sub>3</sub> were investigated by pre-treatment and treatment of 1α,25(OH)<sub>2</sub>D<sub>3</sub> (0.01 to 10 nM) for 48 h in MacCM-stimulated preadipocytes. In parallel, western blotting was used to determine inflammatory signaling molecules including relA of the NF-κB pathway and p44/42 MAPK modified during these processes.<h4>Results</h4>MacCM enhanced the secretion and gene expression of IL-1β, IL-6, IL-8, MCP-1 and RANTES by increasing the phosphorylation levels of relA and p44/42 MAPK in preadipocytes, whereas blocking IL-6 and IL-1β action inhibited the inflammatory responses by decreasing p44/42 MAPK and relA phosphorylation, respectively. Furthermore, 10 nM of 1α,25(OH)<sub>2</sub>D<sub>3</sub> generally inhibited the IL-6 and IL-1β-mediated inflammatory responses, and reduced both p44/42 MAPK and relA phosphorylation in MacCM-stimulated preadipocytes.<h4>Conclusions</h4>1α,25(OH)<sub>2</sub>D<sub>3</sub> attenuates IL-6 and IL-1β-mediated inflammatory responses, probably by inhibiting p44/42 MAPK and relA phosphorylation in MacCM-stimulated human white preadipocytes.

Item Type:	Article
Uncontrolled Keywords:	Human white preadipocytes, Macrophages, IL-6, IL-1, Inflammatory responses, relA, p44, 42 MAPK, 1, 25(OH)(2)D-3
Depositing User:	Symplectic Admin
Date Deposited:	04 Mar 2019 08:17
Last Modified:	19 Jan 2023 00:57
DOI:	10.1186/s13098-019-0405-2
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3033717