The Pharmacologically Active Alkaloid Cryptolepine Activates a Type 1 Interferon Response That Is Independent of MAVS and STING Pathways.

Autor: Domfeh SA; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.; Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences University of Ghana, Legon, Ghana.; Department of Biochemistry and Biotechnology, College of Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Narkwa PW; Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Quaye O; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.; Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences University of Ghana, Legon, Ghana., Kusi KA; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.; Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences University of Ghana, Legon, Ghana.; Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana., Addy BS; Department of Biochemistry and Biotechnology, College of Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Lant S; Department of Microbial Sciences, University of Surrey, Guildford, UK., Sumner RP; Department of Microbial Sciences, University of Surrey, Guildford, UK., Maluquer de Motes C; Department of Microbial Sciences, University of Surrey, Guildford, UK., Awandare GA; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana.; Department of Biochemistry, Cell and Molecular Biology, School of Biological Sciences University of Ghana, Legon, Ghana., Ansah C; Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Mutocheluh M; Department of Clinical Microbiology, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Jazyk: angličtina
Zdroj: Journal of immunology research [J Immunol Res] 2022 Jul 26; Vol. 2022, pp. 8873536. Date of Electronic Publication: 2022 Jul 26 (Print Publication: 2022).
DOI: 10.1155/2022/8873536
Abstrakt: Type 1 interferons (IFN-1) are pleiotropic cytokines with well-established anticancer and antiviral properties, particularly in mucosal tissues. Hence, natural IFN-1-inducing treatments are highly sought after in the clinic. Here, we report for the first time that cryptolepine, a pharmacoactive alkaloid in the medicinal plant Cryptolepis sanguinolenta , is a potent IFN-1 pathway inducer. Cryptolepine increased the transcript levels of JAK1 , TYK2 , STAT1 , STAT2 , IRF9 , and OAS3 , as well as increased the accumulation of STAT1 and OAS3 proteins, similar to recombinant human IFN- α . Cryptolepine effects were observed in multiple cell types including a model of human macrophages. This response was maintained in MAVS and STING-deficient cell lines, suggesting that cryptolepine effects are not mediated by nucleic acids released upon nuclear or organelle damage. In agreement, cryptolepine did not affect cell viability in concentrations that triggered potent IFN-1 activation. In addition, we observed no differences in the presence of a pharmacological inhibitor of TBK1, a pleiotropic kinase that is a converging point for Toll-like receptors (TLRs) and nucleic acid sensors. Together, our results demonstrate that cryptolepine is a strong inducer of IFN-1 response and suggest that cryptolepine-based medications such as C. sanguinolenta extract could be potentially tested in resource-limited regions of the world for the management of chronic viral infections as well as cancers.
Competing Interests: The authors declare that they have no competing interests.
(Copyright © 2022 Seth A. Domfeh et al.)
Databáze: MEDLINE
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