Banca de DEFESA: DÉBORAH CRUZ DOS SANTOS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : DÉBORAH CRUZ DOS SANTOS
DATE: 15/09/2022
TIME: 14:00
LOCAL: https://conferenciaweb.rnp.br/events/defesa-de-tese-deborah-cruz-dos-santos.
TITLE:

Influence of 5α-dihydrotestosterone on the response of murine peritoneal macrophages and human monocytes induced by Staphylococcus aureus

KEY WORDS:

5α-dihydrotestosterone. Staphylococcus aureus. Inflammatory response.

PAGES: 141
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia Geral
SUMMARY:

Introduction: Staphylococcus aureus infections have a high morbidity and mortality rate, considered a major problem for public health. There is little information about the role of dihydrotestosterone in infections caused by S. aureus. Objective: To evaluate the influence of 5α-dihydrotestosterone (DHT) on the response of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (hPMs) in the immune response induced by Staphylococcus aureus. Methodology: An in vitro model was performed from male orchiectomized (OQX) and female BALB/C Shams MPMs and from healthy young male and female MPMs of childbearing age, with sex steroid levels within the normal range. Cells were inoculated with 10μl of S. aureus cap 80 or with sterile saline (control) for a period of 6h. Cells from OQX males, females, male and female hPMs were also pre-treated with a concentration of 100μl (10-2M) of DHT for 24h before stimulation with S. aureus. Cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-10, GM-CSF, total nitrites, hydrogen peroxide (H₂O₂) were measured in culture supernatant. in MPMs and in hPMs. In addition, 84 genes involved in the immune response against S. aureus were analyzed by RT-PCR array. Results: In MPMs, cells inoculated with S. aureus from Sham males showed higher levels of inflammatory cytokines and lower concentrations of IL-10, total nitrites and H₂O₂ compared to OQX. Cells from male Sham inoculated with S. aureus also showed higher concentrations of pro-inflammatory cytokines and lower concentrations of IL-10, total nitrites and H₂O₂ compared to females. In the treatment with DHT, the concentration of inflammatory cytokines and the expression of genes such as TLR-2 and genes involved in the NF-kB pathway were higher in OQX treated with the hormone compared to OQX without pretreatment. In addition, the concentrations of total nitrites and H₂O₂ were lower in pre-treatment cells, both in OQX male and female cells. For the human experiment, all selected research subjects were healthy and sex hormone levels were within the normal range for men and women of childbearing age (17β-estradiol, progesterone, follicle-stimulating hormones (FSH), luteinizing hormones ( LH) and testosterone). hPMs inoculated with S. aureus from men had higher concentrations of inflammatory cytokines and lower concentrations of IL-10, lower levels of total nitrites and H2O2 compared to women. In response to treatment, with DHT, the hormone inhibited the concentrations of total nitrites and H₂O₂ in both men and women, and we observed greater expression of TLR-2 and genes involved in the NF-kB pathway, similar to the results in mice. Conclusion: Our results showed that there is a difference between the sexes in the response to inoculation by S. aureus and that DHT has pro-inflammatory immunomodulatory properties in MPMs and in hPMs. The hormone stimulated greater release of inflammatory cytokines, genes involved in this response, and suppressed the release of important inflammatory markers for phagocytosis against S. aureus. Regarding sex, females performed a better immune defense response against this pathogen. This work presents an approach not presented in the literature, with data on the role of DHT in the inflammatory response against S. aureus, which can be considered important results to generate new studies in androgens and their role in the response against microorganisms, which is of great scientific interest.

BANKING MEMBERS:
Presidente - 1561874 - LUCAS MIRANDA MARQUES
Interno - 2342538 - GUILHERME BARRETO CAMPOS
Interna - 1552395 - TELMA DE JESUS SOARES
Externo ao Programa - 2549111 - RICARDO EVANGELISTA FRAGA
Externa à Instituição - CLARISSA LEAL SILVA E SOUZA