Inflammation

, Volume 35, Issue 1, pp 388–396

Proinflammatory CD14+CD16+ Monocytes are Associated with Microinflammation in Patients with Type 2 Diabetes Mellitus and Diabetic Nephropathy Uremia

  • Mengxue Yang
  • Hua Gan
  • Qing Shen
  • Weixue Tang
  • Xiaogang Du
  • Danyan Chen
Article

Abstract

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-κB 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-κB-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-κB and STAT5 signaling pathways underlying the immune abnormalities of CD14+CD16+ monocytes.

KEY WORDS

type 2 diabetes mellitus diabetic nephropathy uremia microinflammation CD14+CD16+ monocytes Toll-like receptor 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mengxue Yang
    • 1
    • 2
  • Hua Gan
    • 1
  • Qing Shen
    • 1
  • Weixue Tang
    • 3
  • Xiaogang Du
    • 1
  • Danyan Chen
    • 1
  1. 1.Department of NephrologyFirst Affiliated Hospital of ChongQing Medical UniversityChongQingChina
  2. 2.First Affiliated Hospital of Zun Yi Medical CollegeZunYiChina
  3. 3.Department of Pathophysiology, Basic Medical CollegeFirst Affiliated Hospital of ChongQing Medical UniversityChongQingChina

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