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1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes

International Journal of Obesity volume 37, pages 357–365 (2013)Cite this article

Subjects

Abstract

Background:

Adipose tissue expansion during obesity is associated with a state of low-grade inflammation and an increase in macrophage infiltration, which predisposes to insulin resistance and vascular malfunction. Growing evidence suggests that vitamin D3 has immunoregulatory effects and adipose tissue could be a target for vitamin D3 action. Preadipocytes, one of the major cell types in adipose tissue, are actively involved in inflammatory processes.

Objectives:

This study investigated whether the active form of vitamin D3 (1,25(OH)2D3) affects the production of proinflammatory chemokines/cytokines and the monocyte recruitment by human preadipocytes.

Methods/results:

The secretion levels of monocyte chemoattractant proteint-1 (MCP-1), IL-8 and IL-6 were significantly higher in preadipocytes than in differentiated adipocytes, suggesting that preadipocytes could be a major source of proinflammatory mediators. Cytokine profile analysis revealed that 1,25(OH)2D3 (10 nM) markedly reduced the release of MCP-1, IL-6 and IL-8 by preadipocytes. The involvement of NFκB signalling was shown by the upregulation of IκBα protein abundance by 1,25(OH)2D3 in preadipocytes. In addition, 1,25(OH)2D3 was able to decrease the migration of THP-1 monocytes. Treatment with proinflammatory stimuli, including macrophage-conditioned (MC) medium, TNFα and IL-1β, led to a marked increase in protein release of MCP-1 and IL-6 by preadipocytes. Pretreatment with 1,25(OH)2D3 (10 nM and 100 nM) significantly decreased the stimulatory effects of MC medium, TNFα and IL-1β on MCP-1 expression and protein release, although the effect on stimulated release of IL-6 was less potent.

Conclusions:

These results demonstrate that 1,25(OH)2D3 decreases the production of MCP-1 and other proinflammatory mediators by preadipocytes and reduces monocyte migration. Thus, vitamin D3 may protect against adipose tissue inflammation by disrupting the deleterious cycle of macrophage recruitment.

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Acknowledgements

We thank Professor Helen R Griffiths (Aston University, UK) for providing the human THP-1 monocytes. We also thank Dr Adrian O'Hara for IL-1β neutralising antibody. This work was supported by the UK Medical Research Council (G0801226).

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  1. Department of Obesity and Endocrinology, Obesity Biology Research Unit, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK

    D Gao, P Trayhurn & C Bing

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Correspondence to C Bing.

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Gao, D., Trayhurn, P. & Bing, C. 1,25-Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int J Obes 37, 357–365 (2013). https://doi.org/10.1038/ijo.2012.53

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