ArticleMolecular pharmaceutics2015
Phagocytosed Clofazimine Biocrystals Can Modulate Innate Immune Signaling by Inhibiting TNFα and Boosting IL-1RA Secretion.
Article in Molecular pharmaceutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Use of Transcriptional Signatures to Differentiate Pathogen-Specific and Treatment-Specific Host Responses in Patients With Bacterial Bloodstream Infections.The Journal of infectious diseases · 2024Article
- Regulation of cancer stem cells and immunotherapy of glioblastoma (Review).Biomedical reports · 2024Review
- Database screening as a strategy to identify endogenous candidate metabolites to probe and assess mitochondrial drug toxicity.Scientific reports · 2023Article
- Quantitative Raman chemical imaging of intracellular drug-membrane aggregates and small molecule drug precipitates in cytoplasmic organelles.Advanced drug delivery reviews · 2023Review
- Real-World Data Collection from Expanded Access Case Studies for the Treatment of Nontuberculous Mycobacterial Infection with Clofazimine.medRxiv : the preprint server for health sciences · 2023Article
- Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Respirable Clofazimine Particles Produced by Air Jet Milling Technique Are Efficacious in Treatment of BALB/c Mice with Chronic Mycobacterium tuberculosis Infection.Antimicrobial agents and chemotherapy · 2022Article
- Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Review
- Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?Frontiers in immunology · 2021Review
- Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?Pharmaceutics · 2020Review
- Acoustic tweezing cytometry for mechanical phenotyping of macrophages and mechanopharmaceutical cytotripsy.Scientific reports · 2019Article
- Photoacoustic imaging of clofazimine hydrochloride nanoparticle accumulation in cancerous vs normal prostates.PloS one · 2019Article
- Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration.Pharmaceutics · 2018Article
- An Expandable Mechanopharmaceutical Device (1): Measuring the Cargo Capacity of Macrophages in a Living Organism.Pharmaceutical research · 2018Article
- An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.Pharmaceutical research · 2018Article
- DFMG attenuates the activation of macrophages induced by co‑culture with LPC‑injured HUVE‑12 cells via the TLR4/MyD88/NF‑κB signaling pathway.International journal of molecular medicine · 2018Article
- The Physicochemical Basis of Clofazimine-Induced Skin Pigmentation.The Journal of investigative dermatology · 2018Article
- Intestinal Farnesoid X Receptor Activation by Pharmacologic Inhibition of the Organic Solute Transporter α-β.Cellular and molecular gastroenterology and hepatology · 2018Article
- Reverse Engineering the Intracellular Self-Assembly of a Functional Mechanopharmaceutical Device.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Clofazimine (CFZ) is an FDA-approved leprostatic and anti-inflammatory drug that massively accumulates in macrophages, forming insoluble, intracellular crystal-like drug inclusions (CLDIs) during long-term oral dosing. Interestingly, when added to cells in vitro, soluble CFZ is cytotoxic because it depolarizes mitochondria and induces apoptosis. Accordingly, we hypothesized that, in vivo, macrophages detoxify CFZ by sequestering it in CLDIs. To test this hypothesis, CLDIs of CFZ-treated mice were biochemically isolated and then incubated with macrophages in vitro. The cell biological effects of phagocytosed CLDIs were compared to those of soluble CFZ. Unlike soluble CFZ, phagocytosis of CLDIs did not lead to mitochondrial destabilization or apoptosis. Rather, CLDIs altered immune signaling response pathways downstream of Toll-like receptor (TLR) ligation, leading to enhanced interleukin-1 receptor antagonist (IL-1RA) production, dampened NF-κB activation and tissue necrosis factor alpha (TNFα) production, and ultimately decreased TLR expression levels. In aggregate, our results constitute evidence that macrophages detoxify soluble CFZ by sequestering it in a biocompatible, insoluble form. The altered cellular response to TLR ligation suggests that CLDI formation may also underlie CFZ's anti-inflammatory activity.
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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.