Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy.

Publisher: Oxford University Press Country of Publication: England NLM ID: 0057202 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0009-9104 (Print) Linking ISSN: 00099104 NLM ISO Abbreviation: Clin Exp Immunol Subsets: MEDLINE

Publication: 2022- : Oxford : Oxford University Press
Original Publication: Oxford : Blackwell Scientific Publications

Cytokines/*blood ; Diabetes Mellitus, Type 2/*immunology ; Diabetic Nephropathies/*immunology ; Mitogen-Activated Protein Kinases/*blood; Adiponectin/blood ; Adult ; Cells, Cultured ; Chemokines/biosynthesis ; Chemokines/blood ; Cytokines/biosynthesis ; Extracellular Signal-Regulated MAP Kinases/blood ; Female ; Humans ; Interleukin-18/immunology ; Male ; Middle Aged ; Monocytes/enzymology ; Phosphorylation ; T-Lymphocytes, Helper-Inducer/enzymology ; Tumor Necrosis Factor-alpha/immunology ; p38 Mitogen-Activated Protein Kinases/blood

Cytokine-induced inflammation is involved in the pathogenesis of type 2 diabetes mellitus (DM). We investigated plasma concentrations and ex vivo production of cytokines and chemokines, and intracellular signalling molecules, mitogen-activated protein kinases (MAPK) in T helper (Th) cells and monocytes in 94 type 2 diabetic patients with or without nephropathy and 20 healthy controls. Plasma concentrations of inflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-18 and chemokine CCL2 in patients with diabetic nephropathy (DN) were significantly higher than control subjects, while IL-10, CXCL8, CXCL9, CXCL10 and adiponectin concentrations of DN were significantly higher than patients without diabetic nephropathy (NDN) and control subjects (all P < 0.05). Plasma concentrations of TNF-alpha, IL-6, IL-10, IL-18, CCL2, CXCL8, CXCL9, CXCL10 and adiponectin exhibited significant positive correlation with urine albumin : creatinine ratio in DN patients. The percentage increases of ex vivo production of IL-6, CXCL8, CXCL10, CCL2 and CCL5 upon TNF-alpha activation were significantly higher in both NDN and DN patients than controls (all P < 0.05). The percentage increases in IL-18-induced phosphorylation of extracellular signal-regulated kinase (ERK) in Th cells of NDN and DN were significantly higher than controls (P < 0.05), while the percentage increase in TNF-alpha-induced phosphorylation of p38 MAPK in monocytes and IL-18-induced phosphorylation of p38 MAPK in Th cells and monocytes were significantly higher in NDN patients than controls. These results confirmed that the aberrant production of inflammatory cytokines and chemokines and differential activation of MAPK in different leucocytes are the underlying immunopathological mechanisms of type 2 DM patients with DN.

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0 (Adiponectin)
0 (Chemokines)
0 (Cytokines)
0 (Interleukin-18)
0 (Tumor Necrosis Factor-alpha)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)

Date Created: 20070412 Date Completed: 20070823 Latest Revision: 20220409

20221213

PMC1942021

10.1111/j.1365-2249.2007.03389.x

17425653