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
| Autor: | Esther Rodríguez-Gallego, Marta Riera-Borrull, Anna Hernández-Aguilera, Roger Mariné-Casadó, Anna Rull, Raúl Beltrán-Debón, Fedra Luciano-Mateo, Javier A. Menendez, Alejandro Vazquez-Martin, Juan J. Sirvent, Vicente Martín-Paredero, Angel L. Corbí, Elena Sierra-Filardi, Gerard Aragonès, Anabel García-Heredia, Jordi Camps, Carlos Alonso-Villaverde, Jorge Joven |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Mediators of Inflammation, Vol 2013 (2013) |
| Druh dokumentu: | article |
| ISSN: | 0962-9351 1466-1861 |
| DOI: | 10.1155/2013/953841 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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