Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin.

Autor: Mauer J; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany. [4]., Chaurasia B; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2]., Goldau J; Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany., Vogt MC; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Ruud J; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Nguyen KD; Cardiovascular Research Institute, Departments of Physiology and Medicine, University of California, San Francisco, California, USA., Theurich S; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Hausen AC; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Schmitz J; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, Germany. [3] Center for Molecular Medicine Cologne, Cologne, Germany., Brönneke HS; 1] Max Planck Institute for Neurological Research, Cologne, Germany. [2] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Estevez E; Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia., Allen TL; Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia., Mesaros A; Max Planck Institute for Biology of Ageing, Cologne, Germany., Partridge L; Max Planck Institute for Biology of Ageing, Cologne, Germany., Febbraio MA; Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia., Chawla A; Cardiovascular Research Institute, Departments of Physiology and Medicine, University of California, San Francisco, California, USA., Wunderlich FT; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany., Brüning JC; 1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2] Max Planck Institute for Neurological Research, Cologne, Germany. [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Cologne, Germany. [4] Center for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, Germany. [5] Center for Molecular Medicine Cologne, Cologne, Germany.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2014 May; Vol. 15 (5), pp. 423-30. Date of Electronic Publication: 2014 Mar 30.
DOI: 10.1038/ni.2865
Abstrakt: Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that mice with an inactivated gene encoding the IL-6Rα chain of the receptor for IL-6 in myeloid cells (Il6ra(Δmyel) mice) developed exaggerated deterioration of glucose homeostasis during diet-induced obesity, due to enhanced resistance to insulin. Tissues targeted by insulin showed increased inflammation and a shift in macrophage polarization. IL-6 induced expression of the receptor for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6ra(Δmyel) mice were resistant to IL-4-mediated alternative polarization of macrophages and exhibited enhanced susceptibility to lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via IL-6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL-6 in limiting inflammation.
Databáze: MEDLINE