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].
1] Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany. [2].
Nat Immunol. 2014 May;15(5):423-30. doi: 10.1038/ni.2865. Epub 2014 Mar 30.
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.
肥胖和胰岛素抵抗与低度炎症的发展密切相关。白细胞介素 6（IL-6）与肥胖相关的炎症有关；然而，其在这种情况下的作用仍存在争议。在这里，我们发现，骨髓细胞中编码白细胞介素 6 受体（IL-6Rα 链）的基因失活的小鼠（Il6ra(Δmyel) 小鼠）在饮食诱导的肥胖期间，由于对胰岛素的抵抗力增强，葡萄糖稳态恶化加剧。胰岛素作用的组织表现出炎症增加和巨噬细胞极化的转变。IL-6 诱导 IL-4 受体的表达，并以细胞自主的方式增强巨噬细胞对 IL-4 的反应。Il6ra(Δmyel) 小鼠对 IL-4 介导的巨噬细胞替代极化具有抗性，并表现出对脂多糖（LPS）诱导的内毒素血症的易感性增强。我们的结果表明，通过 IL-6 传递的信号是巨噬细胞替代激活的重要决定因素，并赋予 IL-6 在限制炎症中的意想不到的稳态作用。
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