The Role Of Vitamin D Metabolizing Enzymes CYP27B1 And CYP24A1 In Systemic Lupus Erythematosus

Objective:The expression of 1α hydroxylase(CYP27B1),24 hydroxylase(CYP24A1)mRNA and protein,monocyte chemoattractant protein 1(MCP-1)mRNA in peripheral blood mononuclear cells(PBMCs)and serum 25(OH)D of patients with systemic lupus erythematosus(SLE)were detected.To explore the role of CYP27B1and CYP24A1 in SLE,the interaction between vitaminD and CYP27B1,CYP24A1and MCP-1 in immune cells,1α,25 dihydroxyvitamin D3 intervened lipopolysaccharide to stimulate human monocyte(THP-1),then the levels of CYP27B1,CYP24A1,MCP-1 mRNA and MCP-1 in supernatant were detected.Methods:The blood of 77 SLE patients and 35 healthy persons(HC)matched in age and sex in the same season were collected.The expression of CYP27B1,CYP24A1mRNA and protein in PBMCs and MCP-1mRNA in PBMCs were detected.The serum level of 25(OH)D was measured.Intervention of LPS stimulated THP-1 with 1α,25(OH)2D3.After culture for 6h,12h,24h,48h,the supernatant was collected to measure the concentration of MCP-1,the cells were collected to measure the mRNA expression level of CYP24A1,CYP27B1 and MCP-1.Results:The expression level of CYP27B1mRNA in PBMCs of SLE patients was significantly lower than that in HC group(P<0.001),it was also confirmed that SLE patients was lower than that in HC group(P=0.003)by the level of CYP27B1 protein.The incidence of lupus nephritis(41.07%vs 14.28%,P=0.028)and the use rate of glucocorticoids(89.3%vs 47.6%,P<0.0001)in the group with decreased CYP27B1mRNA expression were higher than those normal expressionin SLE.The expression of CYP27B1mRNA was negatively correlated with SLEDAI score(r=-0.331,P=0.003).There was no significant difference in CYP24A1mRNA and protein expression between SLE and HC(P>0.05,P>0.05).The expression level of MCP-1 mRNA in SLE patients was higher than that of HC(P<0.001),while the concentration of serum 25(OH)D was lower than that of HC(37.64±19.89ng/ml,50.58±12.74ng/ml,P=0.003).The expression level of CYP27B1 mRNA increased at 6h and 12h,and the expression level of MCP-1 mRNA and protein increased significantly after LPS stimulated THP-1.The expression level of CYP24A1mRNAwas significantly increased,the expression level of MCP-1 mRNA and protein was decreased after adding la,25(OH)2D3,but the expression level of MCP-1 mRNA did not decrease at 48h(P>0.05).Conclusions:The expression level of CYP27B1 in immune cells of SLE patients may be related to the pathogenesis of SLE,disease activity and lupus nephritis.The use of hormone has some influence on the expression of CYP27B1.The expression of CYP27B1 can be induced by LPS.1α,25(OH))2D3 can inhibit LPS induced MCP-1 gene and protein expression in THP-1 cells,play an anti-inflammatory role,and also induce CYP24A1 gene expression,thus inactivating the activity of 1α,25(OH)2D3 and weakening the anti-inflammatory effect.