PMID- 22322482 OWN - NLM STAT- MEDLINE DCOM- 20120815 LR - 20211021 IS - 1420-908X (Electronic) IS - 1023-3830 (Linking) VI - 61 IP - 5 DP - 2012 May TI - Effects of 1,25-(OH)(2)D (3) on the expressions of vitamin D receptor, STAT5 and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia. PG - 511-20 LID - 10.1007/s00011-012-0441-y [doi] AB - 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. FAU - Yang, Mengxue AU - Yang M AD - Department of Nephrology, First Affiliated Hospital of ChongQing Medical University, ChongQing, China. yangmengxue02@126.com FAU - Shen, Zhaonan AU - Shen Z FAU - Chen, Danyan AU - Chen D FAU - Gan, Hua AU - Gan H FAU - Shen, Qing AU - Shen Q FAU - Yang, Bo AU - Yang B FAU - Du, XiaoGang AU - Du X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120210 PL - Switzerland TA - Inflamm Res JT - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JID - 9508160 RN - 0 (Anti-Inflammatory Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-15) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Calcitriol) RN - 0 (STAT5 Transcription Factor) RN - 0 (STAT5A protein, human) RN - 0 (Tumor Suppressor Proteins) RN - FXC9231JVH (Calcitriol) SB - IM MH - Adult MH - Anti-Inflammatory Agents/*pharmacology MH - Calcitriol/*pharmacology MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis MH - Cytoskeleton/chemistry/*drug effects MH - Diabetes Mellitus, Type 2/*blood MH - Diabetic Nephropathies/*blood MH - Female MH - Humans MH - Interleukin-15/pharmacology MH - Interleukin-6/biosynthesis MH - Lipopolysaccharides/pharmacology MH - Male MH - Microscopy, Fluorescence MH - Middle Aged MH - Monocytes/*drug effects/metabolism MH - Receptors, Calcitriol/*analysis/genetics MH - STAT5 Transcription Factor/*analysis MH - Signal Transduction MH - Tumor Suppressor Proteins/*analysis MH - Uremia/*blood EDAT- 2012/02/11 06:00 MHDA- 2012/08/16 06:00 CRDT- 2012/02/11 06:00 PHST- 2011/10/03 00:00 [received] PHST- 2012/01/20 00:00 [accepted] PHST- 2012/01/05 00:00 [revised] PHST- 2012/02/11 06:00 [entrez] PHST- 2012/02/11 06:00 [pubmed] PHST- 2012/08/16 06:00 [medline] AID - 10.1007/s00011-012-0441-y [doi] PST - ppublish SO - Inflamm Res. 2012 May;61(5):511-20. doi: 10.1007/s00011-012-0441-y. Epub 2012 Feb 10.