4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response.
J Immunol
; 204(9): 2392-2400, 2020 05 01.
Article
in En
| MEDLINE
| ID: mdl-32213561
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Biosynthesis
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Adipose Tissue
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Adaptor Proteins, Signal Transducing
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Interferon Regulatory Factors
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Inflammation
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Macrophages
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2020
Document type:
Article
Affiliation country:
Canadá