Lupus 3.8 X more likely if a poor Vitamin D Receptor
Vitamin D receptor expression in peripheral blood mononuclear cells is inversely associated with disease activity and inflammation in lupus patients.
Clin Rheumatol. 2019 May 18. doi: 10.1007/s10067-019-04594-2.
Sun J1, Liu C2, Zhang S1, Yi B1, Gui M1, Zhang W1, Li YC3, Zhang H4.
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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.
13 studies cited this study as of June 2023
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