ArticleScientific reports2019
Miltefosine increases macrophage cholesterol release and inhibits NLRP3-inflammasome assembly and IL-1β release.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- PPM1A dysfunction aggravates DPN pathology through NF-κB/NLRP3/p-tau axis involving Schwann cell/DRG neuron crosstalk.Journal of translational medicine · 2026Article
- Dysfunction of lipid metabolism and lysosomal capacity: at the core of microglial aging?Frontiers in aging neuroscience · 2026Review
- ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Review
- Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular CaBiomolecules · 2024Review
- In Vitro and Ex Vivo Synergistic Effect of Pyrvinium Pamoate Combined with Miltefosine and Paromomycin againstTropical medicine and infectious disease · 2024Article
- Impavido attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice.iScience · 2023Article
- Myeloid-cell-specific role of Gasdermin D in promoting lung cancer progression in mice.iScience · 2023Article
- Cholesterol metabolism in the regulation of inflammatory responses.Frontiers in pharmacology · 2023Review
- Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis.Advances in experimental medicine and biology · 2023Article
- Reframing the link between metabolism and NLRP3 inflammasome: therapeutic opportunities.Frontiers in immunology · 2023Review
- Autophagy in Atherosclerotic Plaque Cells: Targeting NLRP3 Inflammasome for Self-Rescue.Biomolecules · 2022Review
- Miltefosine as a PPM1A activator improves AD-like pathology in mice by alleviating tauopathy via microglia/neurons crosstalk.Brain, behavior, & immunity - health · 2022Article
- Article
- Insights into inflammasome regulation: cellular, molecular, and pathogenic control of inflammasome activation.Immunologic research · 2022Review
- The anti-parasitic drug miltefosine suppresses activation of human eosinophils and ameliorates allergic inflammation in mice.British journal of pharmacology · 2021Article
- Gasdermin D Mediates Inflammation-Induced Defects in Reverse Cholesterol Transport and Promotes Atherosclerosis.Frontiers in cell and developmental biology · 2021Article
- Article
- Reconciling protective and pathogenic roles of the NLRP3 inflammasome in leishmaniasis.Immunological reviews · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Miltefosine is an FDA approved oral drug for treating cutaneous and visceral leishmaniasis. Leishmania is a flagellated protozoa, which infects and differentiates in macrophages. Here, we studied the effects of Miltefosine on macrophage's lipid homeostasis, autophagy, and NLRP3 inflammasome assembly/activity. Miltefosine treatment conferred multiple effects on macrophage lipid homeostasis leading to increased cholesterol release from cells, increased lipid-raft disruption, decreased phosphatidylserine (PS) flip from the cell-surface, and redistribution of phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane to actin rich regions in the cells. Enhanced basal autophagy, lipophagy and mitophagy was observed in cells treated with Miltefosine vs. control. Miltefosine treated cells showed marked increased in phosphorylation of kinases involved in autophagy induction such as; Adenosine monophosphate-activated protein kinase (AMPK) and Unc-51 like autophagy activating kinase (ULK1). The Toll like receptor (TLR) signaling pathway was blunted by Miltefosine treatment, resulting in decreased TLR4 recruitment to cell-surface and ~75% reduction in LPS induced pro-IL-1β mRNA levels. Miltefosine reduced endotoxin-mediated mitochondrial reactive oxygen species and protected the mitochondrial membrane potential. Miltefosine treatment induced mitophagy and dampened NLRP3 inflammasome assembly. Collectively, our data shows that Miltefosine induced ABCA1 mediated cholesterol release, induced AMPK phosphorylation and mitophagy, while dampening NLRP3 inflammasome assembly and IL-1β release.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.