title: Effect of 1,25-(OH)2D3and lipopolysaccharide on mononuclear cell inflammation in type 2 diabetes mellitus and diabetic nephropathy uremia.
abstract: 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)2D3and 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)2D3treatment 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)2D3partially reversed the effect of LPS and protected patients with T2DM and DNU.
authors.affiliation: Hemopurification Center, Binzhou People's Hospital, Binzhou, China wuelwu@163.com.
authors.forename: E L
authors.initials: EL
authors.lastname: Wu
authors.affiliation: Hemopurification Center, Binzhou People's Hospital, Binzhou, China.
authors.forename: H X
authors.initials: HX
authors.lastname: Cui
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D016022:Case-Control Studies; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018167:Receptors, Calcitriol / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D014511:Uremia / Q000097:blood / Q000276:immunology* / Q000473:pathology
chemical_list: C508609:IL10 protein, human; C569274:IL15 protein, human; C508600:IL6 protein, human; D007106:Immune Sera; D019409:Interleukin-15; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D016753:Interleukin-10; D002117:Calcitriol