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

Bidisha Paul Chowdhury, Shibali Das, Neelam Bodhale, Surya Prakash Pandey, Raki Sudan, Neetu Srivastava, John D. Chisholm, William G. Kerr, Subrata Majumdar, Bhaskar Saha

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number156373
JournalCytokine
Volume171
DOIs
StatePublished - Nov 2023
Externally publishedYes

Keywords

  • 3AC
  • Leishmania
  • Macrophages
  • SHIP1
  • Th1 response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'SHIP1 inhibition via 3-alpha-amino-cholestane enhances protection against Leishmania infection'. Together they form a unique fingerprint.

Cite this