Universität zu Köln

Mauer, Jan ORCID: 0000-0002-0189-5876, Chaurasia, Bhagirath, Goldau, Julia, Vogt, Merly C., Ruud, Johan, Nguyen, Khoa D., Theurich, Sebastian ORCID: 0000-0001-5706-8258, Hausen, A. Christine, Schmitz, Joel, Broenneke, Hella S., Estevez, Emma ORCID: 0000-0002-5125-2190, Allen, Tamara L., Mesaros, Andrea, Partridge, Linda ORCID: 0000-0001-9615-0094, Febbraio, Mark A., Chawla, Ajay, Wunderlich, F. Thomas and Bruening, Jens C. (2014). Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat. Immunol., 15 (5). S. 423 - 434. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1529-2916

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Abstract

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-6R. chain of the receptor for IL-6 in myeloid cells (116ra(Delta myel) 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. 116ra(Delta myel) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mauer, Jan UNSPECIFIED orcid.org/0000-0002-0189-5876 UNSPECIFIED Chaurasia, Bhagirath UNSPECIFIED UNSPECIFIED UNSPECIFIED Goldau, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogt, Merly C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruud, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguyen, Khoa D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Hausen, A. Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Joel UNSPECIFIED UNSPECIFIED UNSPECIFIED Broenneke, Hella S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Estevez, Emma UNSPECIFIED orcid.org/0000-0002-5125-2190 UNSPECIFIED Allen, Tamara L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mesaros, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED Febbraio, Mark A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chawla, Ajay UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-440237
DOI:	10.1038/ni.2865
Journal or Publication Title:	Nat. Immunol.
Volume:	15
Number:	5
Page Range:	S. 423 - 434
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1529-2916
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATIC INFLAMMATION; SKELETAL-MUSCLE; ADIPOSE-TISSUE; DEFICIENT MICE; IKK-BETA; CELLS; INTERLEUKIN-6; METABOLISM; SENSITIVITY; HOMEOSTASIS Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44023