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- Title
Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes.
- Authors
Kokinos, Elena K.; Tsymbal, Sergey A.; Galochkina, Anastasia V.; Bezlepkina, Svetlana A.; Nikolaeva, Julia V.; Vershinina, Sofia O.; Shtro, Anna A.; Tatarskiy, Victor V.; Shtil, Alexander A.; Broude, Eugenia V.; Roninson, Igor B.; Dukhinova, Marina
- Abstract
Hyperactivation of the immune system remains a dramatic, life-threatening complication of viral and bacterial infections, particularly during pneumonia. Therapeutic approaches to counteract local and systemic outbreaks of cytokine storm and to prevent tissue damage remain limited. Cyclin-dependent kinases 8 and 19 (CDK8/19) potentiate transcriptional responses to the altered microenvironment, but CDK8/19 potential in immunoregulation is not fully understood. In the present study, we investigated how a selective CDK8/19 inhibitor, Senexin B, impacts the immunogenic profiles of monocytic cells stimulated using influenza virus H1N1 or bacterial lipopolysaccharides. Senexin B was able to prevent the induction of gene expression of proinflammatory cytokines in THP1 and U937 cell lines and in human peripheral blood-derived mononuclear cells. Moreover, Senexin B substantially reduced functional manifestations of inflammation, including clustering and chemokine-dependent migration of THP1 monocytes and human pulmonary fibroblasts (HPF).
- Subjects
CYCLIN-dependent kinases; INFLUENZA A virus, H1N1 subtype; MONOCYTES; BACTERIOPHAGES; INFLAMMATION; CHEMOKINE receptors; NEURAMINIDASE
- Publication
Viruses (1999-4915), 2023, Vol 15, Issue 6, p1292
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v15061292