PMID- 21847775 OWN - NLM STAT- MEDLINE DCOM- 20120731 LR - 20220408 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 35 IP - 1 DP - 2012 Feb TI - Proinflammatory CD14+CD16+ monocytes are associated with microinflammation in patients with type 2 diabetes mellitus and diabetic nephropathy uremia. PG - 388-96 LID - 10.1007/s10753-011-9374-9 [doi] AB - Diabetic nephropathy (DN) is a major cause of type 2 diabetes mellitus (T2DM) mortality. Innate immunity has been shown to be closely associated with the occurrence and progression of T2DM-associated complications. In this study, we investigated the expression of Toll-like receptor 4 (TLR4) and CD14(+)CD16(+) monocytes in patients with T2DM and DN patients with uremia and TLR4 response to lipopolysaccharide (LPS), and to further explore the potential effects of inflammatory immune response in T2DM and DN uremia. Thirty DN patients with uremia, 28 T2DM patients, and 20 healthy volunteers were enrolled for the determination of CD14(+)CD16(+) fluorescence intensity and TLR4 expression on monocytes by using peripheral blood flow cytometry. Serum C-reactive protein (CRP) level was determined by using the immunoturbidimetry. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with LPS for 24 h. monocytes were collected to detect NF-kappaB p65 and phosphorylated STAT5(p-STAT5) expressions by using Western blotting. Supernatants were sampled for the determination of interleukin-6 (IL-6) concentration by using ELISA. Compared to normal control, T2DM patients and DN uremic patients had a significantly higher CD14(+)CD16(+) fluorescence intensity, TLR4 expression, serum IL-6 and CRP level, whilst these biomarkers were more upregulated in DN uremic patients than in T2DM patients. Following the exposure to LPS, PBMCs showed a significant upregulation in NF-kappaB-p65 and p-STAT5 expression and a remarked increase in Supernatants IL-6 level, in a positive correlation with disease severity. Our results suggest that the disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in T2DM and DN uremic patients. Such immunological dysfunction may be related to the activation of TLR4/NF-kappaB and STAT5 signaling pathways underlying the immune abnormalities of CD14(+)CD16(+) monocytes. FAU - Yang, Mengxue AU - Yang M AD - Department of Nephrology, First Affiliated Hospital of ChongQing Medical University, ChongQing, 400016, China. yangmengxue01@126.com FAU - Gan, Hua AU - Gan H FAU - Shen, Qing AU - Shen Q FAU - Tang, Weixue AU - Tang W FAU - Du, Xiaogang AU - Du X FAU - Chen, Danyan AU - Chen D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Receptors, IgG) RN - 0 (STAT5 Transcription Factor) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (Transcription Factor RelA) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - C-Reactive Protein/analysis MH - Diabetes Mellitus, Type 2/*immunology/metabolism MH - Diabetic Neuropathies/*immunology/metabolism MH - Female MH - Humans MH - Inflammation/*immunology MH - Interleukin-6/biosynthesis MH - Lipopolysaccharide Receptors/*analysis MH - Lipopolysaccharides/immunology MH - Male MH - Monocytes/*immunology MH - NF-kappa B/metabolism MH - Receptors, IgG/*analysis MH - STAT5 Transcription Factor/metabolism MH - Signal Transduction MH - Toll-Like Receptor 4/metabolism MH - Transcription Factor RelA/biosynthesis MH - Uremia/immunology/metabolism EDAT- 2011/08/19 06:00 MHDA- 2012/08/01 06:00 CRDT- 2011/08/18 06:00 PHST- 2011/08/18 06:00 [entrez] PHST- 2011/08/19 06:00 [pubmed] PHST- 2012/08/01 06:00 [medline] AID - 10.1007/s10753-011-9374-9 [doi] PST - ppublish SO - Inflammation. 2012 Feb;35(1):388-96. doi: 10.1007/s10753-011-9374-9.