title: Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.
abstract: Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications.
authors: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany.
authors: Kondaiah
authors: K
authors: Moganti
authors: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany.
authors: Feng
authors: F
authors: Li
authors: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany.
authors: Christina
authors: C
authors: Schmuttermaier
authors: Fifth Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Sarah
authors: S
authors: Riemann
authors: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Friedrich-Ebert Str. 107, D-68167 Mannheim, Germany.
authors: Harald
authors: H
authors: Klüter
authors: Institute of Carcinogenesis, N.N.Blokhin Russian Cancer Research Center, Moscow, Russian Federation; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, 36 Lenin Prospekt, Tomsk 634050, Russian Federation.
authors: Alexei
authors: A
authors: Gratchev
authors: University of Groningen, University Medical Center Groningen, Dept. Pathology and Medical Biology, The Netherlands.
authors: Martin C
authors: MC
authors: Harmsen
authors: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Friedrich-Ebert Str. 107, D-68167 Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, 36 Lenin Prospekt, Tomsk 634050, Russian Federation. Electronic address: julia.kzhyshkowska@medma.uni-heidelberg.de.
authors: Julia
authors: J
authors: Kzhyshkowska
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism; D048909:Diabetes Complications / Q000276:immunology*; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D061251:Primary Cell Culture; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: CCL18; Cytokine; Hyperglycemia; IL-1Ra; IL-1beta; Inflammation; Macrophage; TNF-alpha