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

Rodríguez-Gallego, Esther [et alt.]; 20 p.-11 fig.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. © 2013 Esther Rodríguez-Gallego et al.The Unitat de Recerca Biomédica is part of the Campus of International Excellence Southern Catalonia and is currently being supported by the program of consolidated groups from the Universitat Rovira i Virgili and Grants from the Fondo de Investigación Sanitaria (FIS PI08/1032, PI08/1381, and PI11/2187 PI11/00130). Esther Rodríguez-Gallego is the recipient of a Fellowship from the Generalitat de Catalunya (2012FI B 00389), Marta Riera-Borrull is the recipient of a Fellowship from the Universitat Rovira i Virgili (2010PFRURV-B2-58), and Anabel García-Heredia is the recipient of a Fellowship from Insituto de Salud Carlos III (FI12/00133).Peer reviewe

Ubiquitous transgenic overexpression of C-C Chemokine Ligand 2: A model to Assess the Combined Effect of High Energy Intake and Continous Low-Grade Inflammation

10.1155/2013/953841Excessive 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