Banca de DEFESA: GABRIELA BITTENCOURT GRIMALDI

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : GABRIELA BITTENCOURT GRIMALDI
DATE: 22/07/2022
TIME: 14:00
LOCAL: IGM Sala Virtual 5
TITLE:

STUDY OF THE IMMUNOMODULATORY AND ANTILEISHMANIA ROLE OF FISALIN F IN HUMAN MACROPHAGES

KEY WORDS:

Human macrophage, physalin F, immunomodulation, cutaneous leishmaniasis

PAGES: 77
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUMMARY:

ABSTRACT
INTRODUCTION: Macrophages are important cells in inflammatory processes, and their
deregulation can affect several diseases, such as autoimmune diseases and parasitic diseases.
Leishmaniasis, a group of neglected tropical diseases, is included in this category of diseases.
Cutaneous leishmaniasis is characterized by ulcers in the tegument area and its severity is
related to immunopathogenesis. The available treatment is cytotoxic, associated with
therapeutic failure, parasite resistance, high cost and prolonged administration time. Physalin
F has promising pharmacological properties with potent antileishmanial and
immunomodulatory activity in mice. OBJECTIVE: This study aimed to evaluate the
immunomodulatory role in human macrophages and the anti-Leishmania braziliensis activity
of physalin F in vitro. MATERIAL AND METHODS: Human macrophages were obtained
from PBMC from healthy donors. The dosage of inflammatory cytokines was performed by
the ELISA method in the supernatant of human macrophages stimulated with LPS and with or
without the addition of physalin F and dexamethasone. The cytotoxicity of physalin F on
human macrophages and the viability of L. braziliensis promastigotes were measured using
Alamar Blue®. The action of physalin F on human macrophages was determined after 24
hours of infection with L. braziliensis. Flow cytometry and electron microscopy assays were
performed to evaluate the possible mechanisms of action of physalin F in L. braziliensis
promastigotes. RESULTS: Physalin F reduced the production of the pro-inflammatory
cytokines IL-6, IL-1β and TNF-α by activated macrophages. In the cytotoxicity assays, it
presented a CC50 value of 6.07 ± 1.17 μM. This compound also inhibited the proliferation of
promastigote forms of L. braziliensis, with an IC50 value of 10.85 ± 0.99 μM, and reduced the
number of infected human macrophages and the number of amastigotes per macrophage,
when compared to controls. In promastigotes, the appearance of lipid inclusions, rounding of
the cell body, destruction and loosening of the cell membrane were observed in the
ultrastructural analysis by MEV and MET after treatment with physalin F. Flow cytometry
analyzes indicate that physalin F induces apoptosis in L. braziliensis. CONCLUSIONS:
Physalin F inhibited the activation of human macrophages and promoted an effective anti-L.
braziliensis activity, in both promastigotes and amastigotes.

BANKING MEMBERS:
Interna - 796.762.515-34 - JULIANA PERRONE BEZERRA DE MENEZES FULLAM - UFBA
Presidente - 012.993.637-50 - MILENA BOTELHO PEREIRA SOARES - UFRJ
Interna - 011.952.725-10 - NATALIA MACHADO TAVARES - UFBA