ArticleBiochemical and biophysical research communications2016
Anti-inflammatory activity of chloroquine and amodiaquine through p21-mediated suppression of T cell proliferation and Th1 cell differentiation.
Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 57 citations in OpenAlex.
- A roadmap for understanding sulfadoxine-pyrimethamine in malaria chemoprevention.Parasitology · 2025Review
- Anti-inflammatory effect ofHeliyon · 2024Article
- An Attention towards the Prophylactic and Therapeutic Options of Phytochemicals for SARS-CoV-2: A Molecular Insight.Molecules (Basel, Switzerland) · 2023Review
- Identification of a novel immune-inflammatory signature of COVID-19 infections, and evaluation of pharmacokinetics and therapeutic potential of RXn-02, a novel small-molecule derivative of quinolone.Computers in biology and medicine · 2022Article
- Repurposing Histaminergic Drugs in Multiple Sclerosis.International journal of molecular sciences · 2022Article
- Falciparum but not vivax malaria increases the risk of hypertensive disorders of pregnancy in women followed prospectively from the first trimester.BMC medicine · 2021Article
- The orphan nuclear receptor Nurr1 agonist amodiaquine mediates neuroprotective effects in 6-OHDA Parkinson's disease animal model by enhancing the phosphorylation of P38 mitogen-activated kinase but not PI3K/AKT signaling pathway.Metabolic brain disease · 2021Article
- Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity.Frontiers in pharmacology · 2021Review
- Targeting Crucial Host Factors of SARS-CoV-2.ACS infectious diseases · 2020Review
- Melatonin potentials against viral infections including COVID-19: Current evidence and new findings.Virus research · 2020Review
- SARS-CoV-2, ACE2, and Hydroxychloroquine: Cardiovascular Complications, Therapeutics, and Clinical Readouts in the Current Settings.Pathogens (Basel, Switzerland) · 2020Review
- Autophagy Inhibition Sensitizes Renal Tubular Epithelial Cell to G1 Arrest Induced by Transforming Growth Factor beta (TGF-β).Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Chemical evolution for taming the 'pathogenic kinase' PAK1.Drug discovery today · 2020Article
- PAK1-blockers: Potential Therapeutics against COVID-19.Medicine in drug discovery · 2020Review
- SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions.Viruses · 2020Review
- Rethinking the role of hydroxychloroquine in the treatment of COVID-19.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- Screening for Efficacious Anticonvulsants and Neuroprotectants in Delayed Treatment Models of Organophosphate-induced Status Epilepticus.Neuroscience · 2020Article
- Pharmacokinetics and efficacy of orally administered polymeric chloroquine as macromolecular drug in the treatment of inflammatory bowel disease.Acta biomaterialia · 2018Article
- Enhanced CD25Scientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Chloroquine (CQ) and amodiaquine (AQ) have been used for treating or preventing malaria for decades, and their application has expanded into treating inflammatory disease in humans. CQ and AQ are applicable for controlling rheumatoid arthritis, but their molecular mechanisms of anti-inflammatory activity remain to be elucidated. In this study, we examined the effects of CQ and AQ on T cell activation and T cell-mediated immune response. CQ had no significant effect on T cell numbers, but decreased the population of T cells with a high division rate. However, AQ treatment significantly increased the number of cells with low division rates and eliminated cells with high division rates, resulting in the inhibition of T cell proliferation triggered by T cell receptor stimulation, of which inhibition occurred in developing effector T helper and regulatory T cells, regardless of the different exogenous cytokines. Interestingly, the cyclin-dependent kinase inhibitor p21 was significantly and dose-dependently increased by CQ, and more potently by AQ, while other cell cycle regulators were unchanged. Both CQ and AQ elevated the transcription level of p21 though the activation of p53, but also blocked p21 protein degradation in the presence of cycloheximide, causing p21 protein accumulation mainly in the nucleus. Sustained treatment of developing T cells with either CQ or AQ suppressed IFN-γ production in a dose dependent manner and potently inhibited the differentiation of IFN-γ-producing Th1 cells. These results demonstrate that CQ and AQ increase the expression level of p21 and inhibit T cell proliferation and the development of IFN-γ-producing Th1 cells, thereby revealing beneficial roles in treating a wide range of chronic inflammatory diseases mediated by inflammatory T cells.
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