Vitamin D receptor expression in peripheral blood mononuclear cells is inversely associated with disease activity and inflammation in lupus patients

Clin Rheumatol. 2019 Sep;38(9):2509-2518. doi: 10.1007/s10067-019-04594-2. Epub 2019 May 18.

Abstract

Objective: Systemic lupus erythematosus (SLE) is characterized by uncontrolled production of pro-inflammatory cytokines. Vitamin D receptor (VDR) has potent anti-inflammatory activities. The aim of this study was to examine the correlation between VDR expression and inflammation and disease activity in patients with SLE.

Methods: Ninety-five SLE patients were recruited and divided into two groups, active and inactive, according to their SLE disease activity index (SLEDAI)-2 K, and 40 healthy individuals served as controls. The expression of VDR and NF-κB p65 in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR and Western blotting. VDR expression was correlated with inflammatory and diseases parameters in SLE patients. VDR regulation was also studied in THP-1 and Jurkat cell lines.

Results: PBMC VDR expression was downregulated in SLE patients, especially in the active SLE group. VDR mRNA levels were negatively correlated with SLEDAI-2 K (r = - 0.348, P = 0.001), Systemic Lupus International Collaborating Clinics (SLICC) renal activity scores (r = - 0.346, P = 0.014), and proteinuria (r = - 0.309, P = 0.002) and positively associated with serum complement C3 levels (r = 0.316, P = 0.002). Multiple stepwise regression analysis indicated that PBMC VDR downregulation was an independent risk factor for SLEDAI-2 K. VDR levels were also negatively correlated with NF-κB p65 (r = - 0.339, P = 0.001), TNF-α (r = - 0.268, P = 0.009), and IL-6 (r = - 0.313, P = 0.002) levels. In monocyte and T lymphocyte cell lines, TNF-α suppressed VDR expression, whereas 1,25-dihydroxyvitamin D blocked TNF-α-induced VDR downregulation.

Conclusion: PBMC VDR expression is inversely associated with disease activity and inflammation in SLE patients, and VDR downregulation is likely driven by inflammation.

Keywords: Inflammation; Systemic lupus erythematosus; Vitamin D receptor.

MeSH terms

  • Adult
  • Cell Line
  • Cytokines / metabolism
  • Down-Regulation*
  • Female
  • Humans
  • Inflammation / metabolism
  • Kidney / metabolism
  • Leukocytes, Mononuclear / metabolism*
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Receptors, Calcitriol / metabolism*
  • Severity of Illness Index
  • Signal Transduction / physiology
  • Transcription Factor RelA / metabolism
  • Young Adult

Substances

  • Cytokines
  • Receptors, Calcitriol
  • Transcription Factor RelA