Aintree – 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

Author(s): Zhu J.; Bing C.; Wilding J.P.H.

Source: Diabetology and Metabolic Syndrome; Jan 2019; vol. 11 (no. 1)

Publication Date: Jan 2019

Publication Type(s): Article

Available  at Diabetology and Metabolic Syndrome –  from ProQuest (Hospital Premium Collection) – NHS Version

Available  at Diabetology and Metabolic Syndrome –  from BioMed Central

Available  at Diabetology and Metabolic Syndrome –  from SpringerLink – Medicine

Available  at Diabetology and Metabolic Syndrome –  from Europe PubMed Central – Open Access

Abstract:Background: Metabolic syndrome is characterized by macrophage infiltration and inflammatory responses – metaflammation in adipose tissue. IL-6 and IL-1beta could mediate the inflammatory responses in macrophage stimulated-preadipocytes by modulating MAPK and NF-kappaB pathways. To test this hypothesis we used antibodies to block IL-6 and IL-1beta 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 1alpha,25(OH)2D3 has previously been reported to exert an anti-inflammatory action on macrophage-stimulated adipocytes, in this study we also investigated whether 1alpha,25(OH)2D3 could attenuate inflammatory responses in MacCM-stimulated preadipocytes, and explored the potential anti-inflammatory mechanisms. Method(s): 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-1beta, 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-1beta actions were blocked using IL-6 antibody (300 ng/ml) and IL-1beta antibody (15 mug/ml), respectively. Potential anti-inflammatory effects of 1alpha,25(OH)2D3 were investigated by pre-treatment and treatment of 1alpha,25(OH)2D3 (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-kappaB pathway and p44/42 MAPK modified during these processes. Result(s): MacCM enhanced the secretion and gene expression of IL-1beta, 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-1beta action inhibited the inflammatory responses by decreasing p44/42 MAPK and relA phosphorylation, respectively. Furthermore, 10 nM of 1alpha,25(OH)2D3 generally inhibited the IL-6 and IL-1beta-mediated inflammatory responses, and reduced both p44/42 MAPK and relA phosphorylation in MacCM-stimulated preadipocytes. Conclusion(s): 1alpha,25(OH)2D3 attenuates IL-6 and IL-1beta-mediated inflammatory responses, probably by inhibiting p44/42 MAPK and relA phosphorylation in MacCM-stimulated human white preadipocytes.Copyright © 2019 The Author(s).

Database: EMBASE

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