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Analysis of MEK1/2 and STAT6 impact on macrophage polarization to M2 phenotype, and its influence on the alveolar repair process in mice

Grant number: 18/10177-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2018
Effective date (End): June 30, 2021
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Gustavo Pompermaier Garlet
Grantee:Angelica Cristina Fonseca
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
Associated research grant:15/24637-3 - MSCs and m2 as determinants of the constructive or destructive nature of inflammatory microenvironments associated with bone tissue, AP.TEM

Abstract

Inflammatory process associated with bone tissue, depending on the cell elements involved and mediators produced, may be destructive or constructive. While most of the knowledge of osteoimmunology derives from chronic inflammatory models that characterize 'destructive inflammation', recent studies have advanced the understanding of 'constructive inflammation' associated with tissue repair processes. Macrophages are described as important elements to the repair process and have been characterized in M1 (pro-inflammatory), and M2 (anti-inflammatory and/or pro-reparative) subtypes. However, the exact role of each of these phenotypes, as well as the polarization process to the acquisition of an M1 or M2 phenotype, at the repair sites have not yet been fully determined. In bone repair process, initially the M1 phenotype is predominant, followed by the M2 phenotype. Although the mediators responsible for such phenotypic change in the repair environment are not known (cytokines classical IFNg and IL4 are usually absent in repair sites, in theory, by the non-participation of T cells in this process), the acquisition of M2 phenotype is dependent of specific intracellular pathways, involving signaling molecules such as MEK1/2 and the transcription factor STAT6. In this context, the objective of this project is to evaluate the effect promoted by the pharmacological inhibition of MEK1/2 and STAT6 and to correlate inhibition with the M1/M2 phenotype variation, as well as its impact on the alveolar bone repair process. C57Bl / 6WT mice, submitted to extraction of the upper incisor, under control conditions or treated with drug inhibitors (drug, 10mg /kg /IP), at 24-hour intervals starting one day before the surgical procedure and ending on the day of euthanasia (0, 3, 7 and 14 days). It is believed that from the analyzes, such data will contribute to the clarification of macrophage performance, specifically the M1/M2 phenotypic change, in the alveolar bone repair process, as well as to the understanding of the regulatory mechanisms that act on the bone tissue.