Effect of 1,25-(OH)2D3 and lipopolysaccharide on mononuclear cell inflammation in type 2 diabetes mellitus and diabetic nephropathy uremia.
Genet Mol Res. 2016 Aug 29 ;15(3). Epub 2016 Aug 29. PMID: 27706649
E L Wu
The prevention and treatment of type-2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), which are disorders with high incidence rates, is of primary importance. In this study, we analyzed the effect of 1,25-(OH)2D3 and lipopolysaccharide (LPS) in combination with interleukin (IL)-15 on the inflammatory immune response and expression of vitamin D receptor (VDR) in mononuclear cells of T2DM and DN uremia (DNU) patients. The human acute monocytic leukemia cell line THP-1 was treated with peripheral blood serum isolated from 30 healthy controls and T2DM and DNU patients each, cultured in the presence or absence of 1,25-(OH)2D3, and subsequently treated with LPS and IL-15. The VDR mRNA and protein expression in THP-1 cells was detected by real-time polymerase chain reaction and western blot (and immunofluorescence assay), respectively, and IL-6 and IL-10 concentrations in the culture supernatant were detected by enzyme-linked immunosorbent assay. LPS treatment induced a significant decrease in VDR mRNA expression in T2DM and DNU serum-treated THP-1 cells compared to the control cells (P<0.05). The VDR protein expression in DNU serum-treated THP-1 cells was also significantly down-regulated (P<0.05). LPS treatment induced IL-6 secretion in serum-treated THP-1 cells (P<0.05), while 1,25-(OH)2D3 treatment inhibited IL-6 secretion to some extent. These findings suggested that LPS down-regulates the expression of VDR in mononuclear cells of T2DM and DNU patients and induces an imbalance in the pro-inflammatory and anti-inflammatory cytokine response, while 1,25-(OH)2D3 partially reversed the effect of LPS and protected patients with T2DM and DNU.