SHIP1 inhibition via 3-alpha-amino-cholestane enhances protection against Leishmania infection.

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. Copyright © 2023. Published by Elsevier Ltd.

Citation

Bidisha Paul Chowdhury, Shibali Das, Neelam Bodhale, Surya Prakash Pandey, Raki Sudan, Neetu Srivastava, John D Chisholm, William G Kerr, Subrata Majumdar, Bhaskar Saha. SHIP1 inhibition via 3-alpha-amino-cholestane enhances protection against Leishmania infection. Cytokine. 2023 Nov;171:156373

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PMID: 37776719

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