Analysis of the role of FFAR2 receptor in the inflammation in a DSS-induced colitis model

Author(s)

Sarah de Oliveira

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2021-07-26

Examining board members

Marco Aurélio Ramirez Vinolo; Pedro Manoel Mendes de Moraes Vieira; Caroline Marcantonio Ferreira

• Advisor: Marco Aurélio Ramirez Vinolo

Abstract

Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, through the metabolism of non-digestible carbohydrates from the diet, are molecules that act as signals in microbiota-host interactions. These molecules activate receptors coupled to the G protein, such as FFAR2, which is highly expressed in neutrophils, inducing their chemotaxis, and other effector functions. Studies on the relation of the FFAR2 receptor and intestinal inflammation with FFAR2 knockout (KO) mice, indicate that receptor activation play an important role in the development of inflammatory diseases. However, the mechanisms behind this effect and the target cells are not clearly defined. The aim of this project was to analyze the participation of FFAR2 expressed in neutrophils in intestinal inflammation. For this, it uses mice with conditional deletion of this gene in neutrophils (S100A8Cre+FFAR2fl/fl), in which colitis was induced through the administration of dextran sodium sulfate (DSS) in drinking water. Initially, C57Bl/6 mice were used to determine the best acetate concentration for the treatment of animals, the results obtained showed that the concentration of 150 mM had more evident protective effects on the model. Treatment with acetate, in addition to modulating cells numbers such as neutrophils and Th17 lymphocytes in the colon during colitis, also influence the percentage of neutrophils in bone marrow during inflammation indicating an effect on these cells production/differentiation. Using animals S100A8Cre+FFAR2fl/fl it was possible to observe that the deletion of the receptor in the neutrophils is involved in the protection resulting from the treatment with acetate. Together, our results indicate that FFAR2 activation by acetate in neutrophils participate in the protective effect of this SCFAs in a colitis model (AU)

• FAPESP's process: 19/11662-0 - Participation of the FFAR2 receptor in the inflammation in a DSS-induced colitis model
• Grantee: Sarah de Oliveira
• Support Opportunities: Scholarships in Brazil - Master