@article{916c6d760daf4a97af827baa211ef705,
title = "SHIP1 inhibition via 3-alpha-amino-cholestane enhances protection against Leishmania infection",
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{\textquoteright} 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.",
keywords = "3AC, Leishmania, Macrophages, SHIP1, Th1 response",
author = "Chowdhury, {Bidisha Paul} and Shibali Das and Neelam Bodhale and {Prakash Pandey}, Surya and Raki Sudan and Neetu Srivastava and Chisholm, {John D.} and Kerr, {William G.} and Subrata Majumdar and Bhaskar Saha",
note = "Funding Information: We thank Sandra Fernandes for confirming the anti-SHIP1 activity and potency of 3AC batches used in this study. During the course of this study, it was supported in part by grants from the NIH (R01 HL72523, R01 HL085580, R01 HL107127) and the Paige Arnold Butterfly Run. WGK is the Alfred T. Murphy Family Professor of Children's Oncology Research, an Empire Scholar of the State University of NY. Authors declaration:, Authors declare that they do not have any conflict of interest. William G Kerr and John D Chisholm own patents on SHIPi (Inhibitor of SHIP1). Funding Information: We thank Sandra Fernandes for confirming the anti-SHIP1 activity and potency of 3AC batches used in this study. During the course of this study, it was supported in part by grants from the NIH (R01 HL72523, R01 HL085580, R01 HL107127) and the Paige Arnold Butterfly Run. WGK is the Alfred T. Murphy Family Professor of Children{\textquoteright}s Oncology Research, an Empire Scholar of the State University of NY. Publisher Copyright: {\textcopyright} 2023",
year = "2023",
month = nov,
doi = "10.1016/j.cyto.2023.156373",
language = "English (US)",
volume = "171",
journal = "Cytokine",
issn = "1043-4666",
publisher = "Academic Press Inc.",
}