Vitamin D effects on monocytes' CCL-2, IL6 and CD14 transcription in Addison's disease and HLA susceptibility

J Steroid Biochem Mol Biol. 2018 Mar;177:53-58. doi: 10.1016/j.jsbmb.2017.07.026. Epub 2017 Jul 29.

Abstract

Addison's disease is a rare autoimmune disorder leading to adrenal insufficiency and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms and vitamin D deficiency predispose to Addison's disease. Aim of the current study was, to investigate potential anti-inflammatory vitamin D effects on monocytes in Addison's disease, focusing on inflammatory CCL-2 and IL6, as well on monocyte CD14 markers. Addison's disease is genetically linked to distinct HLA susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for vitamin D effects on monocyte markers. CD14+ monocytes were isolated from Addison's disease patients (AD, n=13) and healthy controls (HC, n=15) and stimulated with 1,25-dihydroxyvitamin D3 and IL1β as an inflammatory stimulant. Cells were processed for mRNA expression of CCL-2, IL6 and CD14 and DNA samples were genotyped for major histocompatibility class (MHC) class II-encoded HLA- DQA1-DQB1 haplotypes. We found a downregulation of CCL-2 after vitamin D treatment in IL1β-stimulated monocytes both from AD patients and HC (AD p<0.001; HC p<0.0001). CD14 expression however, was upregulated in both HC and AD patients after vitamin D treatment (p<0.001, respectively). HC showed higher CD14 transcription level than AD patients after vitamin D treatment (p=0.04). Compared to IL1β-induced inflammation, HC have increased CD14 levels after vitamin D treatment (p<0.001), whereas the IL1β-induced CD14 expression of AD patients' monocytes did not change after vitamin D treatment (p=0.8). AD patients carrying HLA high-risk haplotypes showed an increased CCL-2 expression after IL1β-induced inflammation compared to intermediate-risk HLA carriers (p=0.05). Also HC monocytes' CD14 transcription after IL1β and vitamin D co-stimulation differed according to HLA risk profile. We show that vitamin D can exert anti-inflammatory effects on AD patients' monocytes which may be modulated by HLA risk genotypes.

Keywords: Addison’s disease; CCL-2; CD14; HLA; IL6; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / genetics*
  • Adult
  • Aged
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Chemokine CCL2 / genetics*
  • Female
  • Genotype
  • HLA-DQ alpha-Chains / genetics
  • HLA-DQ beta-Chains / genetics
  • Humans
  • Interleukin-6 / genetics*
  • Lipopolysaccharide Receptors / genetics*
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects
  • Vitamin D / pharmacology*
  • Vitamins / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • CCL2 protein, human
  • Chemokine CCL2
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • IL6 protein, human
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • RNA, Messenger
  • Vitamins
  • Vitamin D