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.
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Change history
17 June 2019
The publisher regret that Funding statement was incomplete in the original publication; the authors have requested that the revised Funding statement be noted.
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Acknowledgments
We thank all of the patients for their participation in this study.
Funding sources
This study was funded by the National Natural Science Foundation of China (No. 81470961 and 2019JJ40463) and the Natural Science Foundation of Hunan Province (NO. 14JJ2037 and 2019JJ40463).
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Sun, J., Liu, C., Zhang, S. et al. Vitamin D receptor expression in peripheral blood mononuclear cells is inversely associated with disease activity and inflammation in lupus patients. Clin Rheumatol 38, 2509–2518 (2019). https://doi.org/10.1007/s10067-019-04594-2
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DOI: https://doi.org/10.1007/s10067-019-04594-2