Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation. (15th December 2013)

• Record Type: Journal Article
• Authors: Rodríguez-Gallego, Esther; Riera-Borrull, Marta; Hernández-Aguilera, Anna; Mariné-Casadó, Roger; Rull, Anna; Beltrán-Debón, Raúl; Luciano-Mateo, Fedra; Menendez, Javier A.; Vazquez-Martin, Alejandro; Sirvent, Juan J.; Martín-Paredero, Vicente; Corbí, Angel L.; Sierra-Filardi, Elena; Aragonès, Gerard; García-Heredia, Anabel; Camps, Jordi; Alonso-Villaverde, Carlos; Joven, Jorge
• Other Names: McCafferty Donna-Marie Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2013(2013)
• Publication Date: 2013-12-15
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2013/953841
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study.