米尔替芬
炎症体
炎症
药理学
肠道菌群
生物
微生物学
免疫学
内脏利什曼病
利什曼病
作者
C. Alicia Traughber,Amanda J Iacano,Kalash Neupane,Mariam R. Khan,Emmanuel Opoku,Tina Nunn,Ashutosh Prince,Naseer Sangwan,Stanley L. Hazen,Jonathan Smith,Kailash Gulshan
出处
期刊:iScience
[Elsevier]
日期:2023-04-01
卷期号:26 (4): 106453-106453
被引量:4
标识
DOI:10.1016/j.isci.2023.106453
摘要
Impavido (Miltefosine) is an FDA-approved drug for treating leishmaniasis and primary amebic meningoencephalitis. We have shown previously that Miltefosine increased cholesterol release and dampened Nlrp3 inflammasome assembly in macrophages. Here, we show that Miltefosine reduced LPS-induced choline uptake by macrophages, and attenuated Nlrp3 inflammasome assembly in mice. Miltefosine-fed mice showed reduced plasma IL-1β in a polymicrobial cecal slurry model of systemic inflammation. Miltefosine-fed mice showed increased reverse cholesterol transport to the plasma, liver, and feces. Hyperlipidemic apoE−/− mice fed with WTD + Miltefosine showed significantly reduced weight gain and markedly reduced atherosclerotic lesions versus mice fed with WTD. The 16S rDNA sequencing and analysis of gut microbiota showed marked alterations in the microbiota profile of Miltefosine-fed hyperlipidemic apoE−/− versus control, with the most notable changes in Romboutsia and Bacteriodes species. Taken together, these data indicate that Miltefosine causes pleiotropic effects on lipid metabolism, inflammasome activity, atherosclerosis, and the gut microbiota.
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