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STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis
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SYSNO ASEP 0556396 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title STING Agonist-Mediated Cytokine Secretion Is Accompanied by Monocyte Apoptosis Author(s) Pimková Polidarová, Markéta (UOCHB-X) ORCID
Břehová, Petra (UOCHB-X) RID, ORCID
Dejmek, Milan (UOCHB-X) RID, ORCID
Birkuš, Gabriel (UOCHB-X) ORCID
Brázdová, Andrea (UOCHB-X) ORCIDSource Title ACS Infectious Diseases. - : American Chemical Society - ISSN 2373-8227
Roč. 8, č. 3 (2022), s. 463-471Number of pages 9 s. Language eng - English Country US - United States Keywords STING ; cGAS-STING pathway ; apoptosis ; monocytes ; proinflammatory cytokines ; interferons OECD category Biochemistry and molecular biology R&D Projects EF16_019/0000729 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 UT WOS 000772168200009 EID SCOPUS 85125037291 DOI 10.1021/acsinfecdis.1c00554 Annotation The cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway plays a crucial role in inducing an antiviral and antitumor immune response. We studied the effects of synthetic STING agonists on several immune populations and related cytokine production. In comparison with the toll-like receptor 7 (TLR7) agonist, STING agonists induced secretion of a broader proinflammatory cytokine spectrum. Unlike the TLR7 agonist, the structurally diverse STING agonists partially depleted B and NK cells and completely depleted CD14+ monocytes via induction of apoptosis. The TANK-binding kinase 1 inhibitor efficiently prevented interferon alpha (IFN alpha) secretion and cell depletion, suggesting their possible dependence on the cGAS-STING pathway activation. Finally, IFN alpha, tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta secretion and CD14+ monocyte apoptosis were primary responses to STING agonists, whereas IFN gamma was secreted secondarily. These findings bring new insights into the cGAS-STING pathway immunomodulation that is of future therapeutic importance. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2023 Electronic address https://doi.org/10.1021/acsinfecdis.1c00554
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