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Production of PGE2 by dendritic cells front phagocytosis of infected apoptotic cells

Grant number: 11/23788-7
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2013
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Alexandra Ivo de Medeiros
Grantee:Amanda Correia Saraiva
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

During apoptosis process, in contrast to necrosis one, the cellular permeability is maintained avoiding the liberation of intracellular components (named DAMPS - Damage Associated Molecular Patterns) which can initiate the production of inflammatory mediators by phagocytes. The ingestion of apoptotic cells, or even the interaction of them with macrophages, promotes the release of anti-inflammatory molecules such as TGF-², IL-10, nitric oxide, prostaglandin E2 (PGE2) and platelet activation factor (PAF), while inhibits the production of pro-inflammatory mediators, such as TNF-±, IL-1, KC, IL-8 and leukotriene C4.Though, the phagocytosis of infected apoptotic cells, which means cells containing associated PAMP, promotes the production of mediators such as IL-23, TGF-² and IL-6 by dendritic cells. This production fits the specific conditions to generate Th17 cells and reveals such a new physiologic mechanism for this cell generation.The role of PGE2 in adaptive immunity has been investigated concerning differentiation and activation of Th1, Treg and Th17 lymphocytes. As far as now, nothing is known about the participation of this lipid mediator in the context of phagocytosis of infected apoptotic cells and the mechanism by which PGE2 can synergistically collaborate to TGF-², IL-6 and IL-23 in the process of Th17 cells differentiation.The hypothesis of this study grounds on the study of PGE2 production by dendritic cells during phagocytosis of infected apoptotic cells and generation of conditioned medium for the study of the role of PGE2 in Th17 differentiation.