OBJECTIVE: To explore the effects of 1,25-(OH)(2)D(3) and lipopolysaccharide (LPS) plus human recombinant interleukin-15 (IL-15) on expression of vitamin D receptor (VDR) and STAT5, and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes (T2DM) patients and diabetic nephropathy (DN) patients with uremia. MATERIALS AND METHODS: Peripheral sera were isolated from healthy volunteers (control group, T2DM patients and DN uremic non-dialysis patients). After incubation with or without 1,25(OH)(2)D(3), THP-1 monocytes were treated with LPS plus IL-15 prior to the collection of cells and supernatants. VDR mRNA transcription was examined by RT-PCR, whilst THP-1 monocytic VDR, STAT5 and p-STAT5 expressions were investigated by Western blotting. Concentrations of IL-6 and monocyte chemoattractant protein-1 (MCP-1) in supernatants were assessed by ELISA. Immunofluorescence and a laser confocal microscopy was used to examine the expression of VDR and cytoskeletal proteins. RESULTS: Compared to the normal control, LPS and IL-15 down-regulate monocytic VDR expression in T2DM patients and DN uremic patients, whilst with cytoskeletal rearrangement, they up-regulate p-STAT5 expression as well as IL-6 and MCP-1 activity. Such effects could be in part blocked by 1,25-(OH)(2)D(3). CONCLUSION: The above results suggest that the anti-inflammatory mechanism of 1,25-(OH)(2)D(3) may be related to cytoskeletal proteins, VDR and STAT5 signaling pathway.
OBJECTIVE: To explore the effects of 1,25-(OH)(2)D(3) and lipopolysaccharide (LPS) plus human recombinant interleukin-15 (IL-15) on expression of vitamin D receptor (VDR) and STAT5, and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes (T2DM) patients and diabetic nephropathy (DN) patients with uremia. MATERIALS AND METHODS: Peripheral sera were isolated from healthy volunteers (control group, T2DM patients and DN uremic non-dialysis patients). After incubation with or without 1,25(OH)(2)D(3), THP-1 monocytes were treated with LPS plus IL-15 prior to the collection of cells and supernatants. VDR mRNA transcription was examined by RT-PCR, whilst THP-1 monocytic VDR, STAT5 and p-STAT5 expressions were investigated by Western blotting. Concentrations of IL-6 and monocyte chemoattractant protein-1 (MCP-1) in supernatants were assessed by ELISA. Immunofluorescence and a laser confocal microscopy was used to examine the expression of VDR and cytoskeletal proteins. RESULTS: Compared to the normal control, LPS and IL-15 down-regulate monocytic VDR expression in T2DM patients and DN uremic patients, whilst with cytoskeletal rearrangement, they up-regulate p-STAT5 expression as well as IL-6 and MCP-1 activity. Such effects could be in part blocked by 1,25-(OH)(2)D(3). CONCLUSION: The above results suggest that the anti-inflammatory mechanism of 1,25-(OH)(2)D(3) may be related to cytoskeletal proteins, VDR and STAT5 signaling pathway.
Authors: Pulak Tripathi; Sema Kurtulus; Sara Wojciechowski; Allyson Sholl; Kasper Hoebe; Suzanne C Morris; Fred D Finkelman; H Leighton Grimes; David A Hildeman Journal: J Immunol Date: 2010-07-19 Impact factor: 5.422
Authors: Guadalupe Ortiz-Muñoz; Virginia Lopez-Parra; Oscar Lopez-Franco; Paula Fernandez-Vizarra; Beñat Mallavia; Claudio Flores; Ana Sanz; Julia Blanco; Sergio Mezzano; Alberto Ortiz; Jesus Egido; Carmen Gomez-Guerrero Journal: J Am Soc Nephrol Date: 2010-02-25 Impact factor: 10.121
Authors: S J Creely; P G McTernan; C M Kusminski; ff M Fisher; N F Da Silva; M Khanolkar; M Evans; A L Harte; S Kumar Journal: Am J Physiol Endocrinol Metab Date: 2006-11-07 Impact factor: 4.310