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Role of GPR43 on macrophage function: possible mechanism of action of short-chain fatty acids

Grant number: 06/00372-1
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2006
Effective date (End): December 31, 2010
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Rui Curi
Grantee:Marco Aurélio Ramirez Vinolo
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

G protein coupled receptors represent the largest family of transmembrane receptors and they are responsible for the intracellular propagation of signals in response to various stimuli. The GPR 40, 41 and 43 receptors belong to a subfamily of GPRs activated by fatty acids. The GPR43 receptor is expressed in leukocytes, mainly monocytes and neutrophils, being activated by short chain fatty acids (SCFA). SCFAs, mainly propionate and butyrate, have marked effects on leukocyte differentiation, maturation and activation. The aim of this study was to evaluate the importance of GPR43 activation to control macrophage function. For this purpose, THP-1 cells (acute promielocytic leukemia cells) differentiated into macrophages will be treated with SCFAs (acetate, propionate and butyrate). The following functional parameters will be examined: chemiotaxis, phagocytic capacity, production of reactive oxygen species, nitric oxide and citokines (TNF- α, IL-1β, INF- γ, IL-6 and IL-10), activation of the transcription receptor NFκB and expression of CD14 and Toll Like Receptor 4 (TLR 4). The GPR43 expression will be blocked using siRNA (small interference RNA) and the functional parameters above described will be measured after the treatment with the SCFAs. The effect of GPR43 will then be determined. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VINOLO, MARCO A. R.; RODRIGUES, HOSANA G.; HATANAKA, ELAINE; HEBEDA, CRISTINA B.; FARSKY, SANDRA H. P.; CURI, RUI. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clinical Science, v. 117, n. 9-10, p. 331-338, NOV 2009. Web of Science Citations: 62.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
VINOLO, Marco Aurélio Ramirez. Efeito dos ácidos graxos de cadeia curta sobre neutrófilos.. 2010. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.

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