Banca de QUALIFICAÇÃO: Andréia Cristina Gonçalves Cascaes

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : Andréia Cristina Gonçalves Cascaes
DATE: 14/02/2023
TIME: 15:00
LOCAL: Plataforma Teams
TITLE:

IMMUNOMODULATORY EFFECT OF ANACARDIC ACID IN MICROGLIA STIMULATED BY PLASMODIUM PARASITED ERYTHROCYTES 

KEY WORDS:

Malaria, Anacardic Acid, Microglia, NFkB, eicosanoids, cytokines, oxygen radicals, nitrogen radicals.

PAGES: 59
BIG AREA: Ciências da Saúde
AREA: Medicina
SUBÁREA: Clínica Médica
SPECIALTY: Doenças Infecciosas e Parasitárias
SUMMARY:

Introduction:  It is estimated that in the year 2020 there were about 241 million cases of malaria in the world. Among the severe forms of the disease, the cerebral form is one of the most important, and the imbalance between pro and anti-inflammatory cytokines resulting in the dysregulation of the immune system is part of its immunopathogenesis. The activation of the NF-kB pathway regulate and modulate inflammatory processes of the immune response. Its activation occurs in two different ways: canonical and non-canonical. Peroxisomal proliferated gamma receptors (PPAR-g) belong to a family of nuclear receptors and have the function of regulating important genes and, when activated, suppress genes involved in the secretion of pro-inflammatory cytokines, thus showing potential to control the hyperactivation of the immune system that occurs during Plasmodium infection, and promotes the maintenance of endothelial integrity. Anacardic acid is a molecule with partial agonist activity of PPAR-𝛾, interacts indirectly with the NF-kB pathway, showing potential to prevent severe forms of malaria. This work aims to evaluate the immunomodulatory effect of anacardic acid on murine microglia lineage BV-2 in the presence of Plasmodium berghei ANKA and on human microglia lineage C20 in the presence of Plasmodium falciparum. Materials and Methods: These groups were evaluated: basal control, treated with anacardic acid, incubated with non-parasitized or parasitized erythrocytes and incubated with non-parasitized or parasitized erythrocytes and treated or not with anacardic acid. We evaluated in BV-2 microglia stimulated in vitro with P. berghei ANKA the influence of anacardic acid on the production of reactive oxygen and nitrogen species, the expression of rel-A and rel-B molecules of the NF-kB pathway, the production of the chemokine MCP-1 and the cytokine IL-6, and the expression of COX-2 and 5-LOX. For the experiments with the C-20 microglia it is intended to evaluate some functions of the immune system. Pertinent statistical tests were performed. Results: Treatment with anacardic acid of BV-2 microglia previously incubated with Plasmodium-parasitized erythrocytes significantly increased rel A expression compared to cells incubated with untreated parasitized erythrocytes. The treatment also increased rel-B production in BV-2 cells incubated with parasitized red blood cells. In the expression of the COX-2 enzyme, the opposite occurred. The expression of the 5-LOX enzyme was reduced with the use of anacardic acid, but the treatment did not modify its expression. Treatment with anacardic acid decreased the expression of reactive oxygen species, and in reactive nitrogen species there was a decrease in production by treating BV-2 cells incubated with parasitized red blood cells. Anacardic acid decreased MCP-1 expression. The same occurred in the treatment of BV-2 cells incubated with non-parasitized red blood cells. Incubation with parasitized red blood cells increased IL-6 production.  Conclusions: Anacardic acid increased rel-A production, decreased COX-2 production, decreased 5-LOX, ROS and MCP-1 expression compared to basal production. Non-parasitized RBCs along with anacardic acid treatment also decreased MCP-1 expression. Anacardic acid decreased the expression of ERNs compared to cells stimulated only with parasitized red blood cells. Parasitized red blood cells increase IL-6 expression. These data suggest that anacardic acid may play a role as an adjuvant molecule to antiparasitic drugs for the prevention of severe forms of malaria.

BANKING MEMBERS:
Interno - 2243078 - LUIZ ANTONIO SOARES ROMEIRO
Presidente - 6404463 - MARIA IMACULADA MUNIZ BARBOZA JUNQUEIRA
Externa à Instituição - SHIRLEY CLAUDINO PEREIRA COUTO - UnB
Externa à Instituição - THAIS TAMARA CASTRO E SOUZA MINUZZI - MS