SHIP1 inhibition via 3-alpha-amino-cholestane enhances protection against Leishmania infection.
Cytokine
; 171: 156373, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37776719
ABSTRACT
Leishmania major and L. donovani cause cutaneous leishmaniasis and visceral leishmaniasis, respectively. Available chemotherapies suffer from toxicity, drug-resistance or high cost of production prompting the need for the discovery of new anti-leishmanials. Here, we test a novel aminosteriodal compound- 3-alpha-amino-cholestane [3AC] - that shows selective inhibition of SHIP1, an inositol-5'-phosphate-specific phosphatase with potent effects on the immune system. We report that 3AC-sensitive SHIP1 expression increases in Leishmania-infected macrophages. Treatment of BALB/c mice, a Leishmania-susceptible host, with 3AC increased anti-leishmanial, but reduced pro-leishmanial, cytokines' production and reduced the parasite load in both L. major and L. donovani infections. These findings implicate SHIPi as a potential novel immunostimulant with anti-leishmanial function.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leishmania donovani
/
Leishmaniose Visceral
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article