4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response.

Autor:	Pearl D; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Katsumura S; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229., Amiri M; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Tabatabaei N; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612., Zhang X; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Vinette V; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Pang X; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612., Beug ST; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada., Kim SH; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Jones LM; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Robichaud N; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Ong SG; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612.; Division of Cardiology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612., Jia JJ; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada., Ali H; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada., Tremblay ML; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Jaramillo M; Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada; and., Alain T; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada., Morita M; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229; moritam@uthscsa.edu nahum.sonenberg@mcgill.ca sorousht@uic.edu.; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.; Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan., Sonenberg N; Rosalind and Morris Goodman Cancer Research Center, McGill University, Montreal, Quebec H3A 1A3, Canada; moritam@uthscsa.edu nahum.sonenberg@mcgill.ca sorousht@uic.edu.; Department of Biochemistry, McGill University, Montreal, Quebec H3A 1A3, Canada., Tahmasebi S; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612; moritam@uthscsa.edu nahum.sonenberg@mcgill.ca sorousht@uic.edu.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 May 01; Vol. 204 (9), pp. 2392-2400. Date of Electronic Publication: 2020 Mar 25.
DOI:	10.4049/jimmunol.1900538
Abstrakt:	Deregulation of mRNA translation engenders many human disorders, including obesity, neurodegenerative diseases, and cancer, and is associated with pathogen infections. The role of eIF4E-dependent translational control in macrophage inflammatory responses in vivo is largely unexplored. In this study, we investigated the involvement of the translation inhibitors eIF4E-binding proteins (4E-BPs) in the regulation of macrophage inflammatory responses in vitro and in vivo. We show that the lack of 4E-BPs exacerbates inflammatory polarization of bone marrow-derived macrophages and that 4E-BP-null adipose tissue macrophages display enhanced inflammatory gene expression following exposure to a high-fat diet (HFD). The exaggerated inflammatory response in HFD-fed 4E-BP-null mice coincides with significantly higher weight gain, higher Irf8 mRNA translation, and increased expression of IRF8 in adipose tissue compared with wild-type mice. Thus, 4E-BP-dependent translational control limits, in part, the proinflammatory response during HFD. These data underscore the activity of the 4E-BP-IRF8 axis as a paramount regulatory mechanism of proinflammatory responses in adipose tissue macrophages. (Copyright © 2020 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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