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

• Published in: Clinical and experimental immunology Vol. 149; no. 1; pp. 123 - 131
• Main Authors: Wong, C.K, Ho, A.W.Y, Tong, P.C.Y, Yeung, C.Y, Kong, A.P.S, Lun, S.W.M, Chan, J.C.N, Lam, C.W.K
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.07.2007; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Adiponectin; Adiponectin - blood; Adult; Analytical, structural and metabolic biochemistry; Biological and medical sciences; biosynthesis; blood; Cells, Cultured; Chemokines; Chemokines - biosynthesis; Chemokines - blood; chemokines/monokines; Cytokines; Cytokines - biosynthesis; Cytokines - blood; cytokines/interleukins; diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - immunology; Diabetic Nephropathies; Diabetic Nephropathies - immunology; enzymology; Extracellular Signal-Regulated MAP Kinases; Extracellular Signal-Regulated MAP Kinases - blood; Female; Fundamental and applied biological sciences. Psychology; Humans; immunology; Interleukin-18; Interleukin-18 - immunology; kinases/phosphatases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases - blood; Molecular biophysics; Monocytes; Monocytes - enzymology; p38 Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases - blood; Phosphorylation; renal immunology/disease; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Helper-Inducer - enzymology; Translational Studies; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - immunology; Endocrinopathy; Type 2 diabetes; chemokines/monokines; kinases/ phosphatases; Interleukin; Phosphoric monoester hydrolases; Monokine; Esterases; Activation; Biochemistry; Immunology; Anomaly; cytokines/interleukins; Human; Kidney disease; Urinary system disease; Enzyme; Transferases; Cytokine; Mitogen-activated protein kinase; renal immunology/disease; Metabolic diseases; Biophysics; Chemokine; Nephropathy; Kinase; Hydrolases; Molecular biology; diabetes
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2007.03389.x

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)-α, 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-α, 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-α 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-α-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.