Plitidepsin as an Immunomodulator against Respiratory Viral Infections.

Autor:	Losada A; Department of Research and Development, PharmaMar S.A., Colmenar Viejo, Madrid, Spain., Izquierdo-Useros N; IrsiCaixa AIDS Research Institute, Badalona, Spain.; Germans Trias i Pujol Research Institute, Can Ruti Campus, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain., Aviles P; Department of Research and Development, PharmaMar S.A., Colmenar Viejo, Madrid, Spain., Vergara-Alert J; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Latino I; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Bellinzona, Switzerland., Segalés J; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Gonzalez SF; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Bellinzona, Switzerland., Cuevas C; Department of Research and Development, PharmaMar S.A., Colmenar Viejo, Madrid, Spain., Raïch-Regué D; IrsiCaixa AIDS Research Institute, Badalona, Spain., Muñoz-Alonso MJ; Department of Research and Development, PharmaMar S.A., Colmenar Viejo, Madrid, Spain., Perez-Zsolt D; IrsiCaixa AIDS Research Institute, Badalona, Spain., Muñoz-Basagoiti J; IrsiCaixa AIDS Research Institute, Badalona, Spain., Rodon J; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Chang LA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Warang P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Singh G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Brustolin M; Unit of Entomology, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium., Cantero G; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Roca N; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Pérez M; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Bustos-Morán E; Department of Research and Development, PharmaMar S.A., Colmenar Viejo, Madrid, Spain., White K; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY., Schotsaert M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.; The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Apr 15; Vol. 212 (8), pp. 1307-1318.
DOI:	10.4049/jimmunol.2300426
Abstrakt:	Plitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2. In resiquimod (a ligand of TLR7/8)-stimulated THP1 human monocytes, plitidepsin-mediated reductions of IL-6 mRNA and IL-6 levels were also noticed. Additionally, although resiquimod-induced binding to DNA of NF-κB family members was unaffected by plitidepsin, a decrease in the regulated transcription by NF-κB (a key transcription factor involved in the inflammatory cascade) was observed. Furthermore, the phosphorylation of p65 that is required for full transcriptional NF-κB activity was significantly reduced by plitidepsin. Moreover, decreases of IL-6 levels and other proinflammatory cytokines were also seen in either SARS-CoV-2 or H1N1 influenza virus-infected mice, which were treated at low enough plitidepsin doses to not induce antiviral effects. In summary, plitidepsin is a promising therapeutic agent for the treatment of viral infections, not only because of its host-targeted antiviral effect, but also for its immunomodulatory effect, both of which were evidenced in vitro and in vivo by the decrease of proinflammatory cytokines. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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