ArticleBritish journal of pharmacology2009
The impact of cytokines on the expression of drug transporters, cytochrome P450 enzymes and chemokine receptors in human PBMC.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
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- Disease-drug and drug-drug interaction in COVID-19: Risk and assessment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients.European journal of drug metabolism and pharmacokinetics · 2021Review
- CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations-Implication for Drug Safety, Dosing, and Individualized Therapy.Frontiers in genetics · 2021Review
- Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms.Medical hypotheses · 2020Article
- Role of HIV and Antiretroviral Therapy on the Expression of Placental Transporters in Women with HIV.The AAPS journal · 2020Article
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- The impact of liver transplant recipient and donor genetic variability on tacrolimus exposure and transplant outcome.British journal of clinical pharmacology · 2019Article
- Alcohol and Cocaine Exposure Modulates ABCB1 and ABCG2 Transporters in Male Alcohol-Preferring Rats.Molecular neurobiology · 2019Article
- Evaluation of Potential Disease-Mediated Drug-Drug Interaction in Patients With Moderate-to-Severe Atopic Dermatitis Receiving Dupilumab.Clinical pharmacology and therapeutics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeThe function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC. EXPERIMENTAL APPROACH: Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes. KEY
resultsWe show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 +/- 11961) and protein (% control 200 +/- 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-gamma (IFNgamma) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNgamma respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r(2) = 0.545). CONCLUSIONS AND IMPLICATIONS: These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.
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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.