Role of short chain fatty acids and their receptor (GPR43) in the immune response ...
| Grant number: | 14/02560-6 |
| Support type: | Scholarships in Brazil - Master |
| Effective date (Start): | August 01, 2014 |
| Effective date (End): | January 31, 2017 |
| Field of knowledge: | Biological Sciences - Physiology - General Physiology |
| Principal Investigator: | Marco Aurélio Ramirez Vinolo |
| Grantee: | Renan Oliveira Corrêa |
| Home Institution: | Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Associated research grant: | 12/10653-9 - Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro, AP.JP |
| Associated scholarship(s): | 15/14105-4 - Role of the epigenetic changes induced by SCFAs in intestinal epithelial cells, BE.EP.MS |
Abstract Short-chain fatty acids (SCFAs) such as butyrate, propionate and acetate are products of the dietary fibers fermentation from anaerobic bacteria in the gastrointestinal tract. These compounds, besides being an important energetic substrate, have many other actions in the organism including regulation of cellular differentiation, proliferation, apoptosis, and activation of the inflammatory/immune response. Part of these actions is due to the binding of the SCFAs to G protein-coupled receptors as the GPR43, a membrane receptor expressed on the immune cells, mainly on neutrophils. It is proven the involvement of the GPR43 in the chemotactic effect of the SCFAs in neutrophils and its participation in the recruitment of these cells in inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. However, the understanding about the mechanisms of action of this receptor and its relevance in infectious conditions by anaerobic bacteria (SCFAs producers) is still very limited. Thus, our aim is to test the interference of the SCFAs in the leukocyte migration and effective function in response to an in vivo mono-infection of Aggregatibacter actinomycetemcomitans using a subcutaneous chamber model. Specifically, we will evaluate cytokines and inflammatory mediators, leukocyte recruitment, bacterial killing capacity, as well as the expression of inflammatory markers in this model. Moreover, we will verify the involvement of the GPR43 receptor in the observed effects using knockout animals for GPR43 and, depending of the obtained results, in chimera mice (wild type animals transplanted with the bone marrow of knockout animals and vice-verse). | |