Plitidepsin as an Immunomodulator against Respiratory Viral Infections
Copyright © 2024 by The American Association of Immunologists, Inc..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:212 |
---|---|
Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 212(2024), 8 vom: 15. Apr., Seite 1307-1318 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Losada, Alejandro [VerfasserIn] |
---|
Links: |
---|
Themen: |
Antiviral Agents |
---|
Anmerkungen: |
Date Completed 03.04.2024 Date Revised 05.04.2024 published: Print Citation Status MEDLINE |
---|
doi: |
10.4049/jimmunol.2300426 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM369059638 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM369059638 | ||
003 | DE-627 | ||
005 | 20240405233649.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240229s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.4049/jimmunol.2300426 |2 doi | |
028 | 5 | 2 | |a pubmed24n1366.xml |
035 | |a (DE-627)NLM369059638 | ||
035 | |a (NLM)38416036 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Losada, Alejandro |e verfasserin |4 aut | |
245 | 1 | 0 | |a Plitidepsin as an Immunomodulator against Respiratory Viral Infections |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 03.04.2024 | ||
500 | |a Date Revised 05.04.2024 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2024 by The American Association of Immunologists, Inc. | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 7 | |a NF-kappa B |2 NLM | |
650 | 7 | |a plitidepsin |2 NLM | |
650 | 7 | |a Y76ID234HW |2 NLM | |
650 | 7 | |a Interleukin-6 |2 NLM | |
650 | 7 | |a Antiviral Agents |2 NLM | |
650 | 7 | |a Immunologic Factors |2 NLM | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a Depsipeptides |2 NLM | |
700 | 1 | |a Izquierdo-Useros, Nuria |e verfasserin |4 aut | |
700 | 1 | |a Aviles, Pablo |e verfasserin |4 aut | |
700 | 1 | |a Vergara-Alert, Júlia |e verfasserin |4 aut | |
700 | 1 | |a Latino, Irene |e verfasserin |4 aut | |
700 | 1 | |a Segalés, Joaquim |e verfasserin |4 aut | |
700 | 1 | |a Gonzalez, Santiago F |e verfasserin |4 aut | |
700 | 1 | |a Cuevas, Carmen |e verfasserin |4 aut | |
700 | 1 | |a Raïch-Regué, Dàlia |e verfasserin |4 aut | |
700 | 1 | |a Muñoz-Alonso, María J |e verfasserin |4 aut | |
700 | 1 | |a Perez-Zsolt, Daniel |e verfasserin |4 aut | |
700 | 1 | |a Muñoz-Basagoiti, Jordana |e verfasserin |4 aut | |
700 | 1 | |a Rodon, Jordi |e verfasserin |4 aut | |
700 | 1 | |a Chang, Lauren A |e verfasserin |4 aut | |
700 | 1 | |a Warang, Prajakta |e verfasserin |4 aut | |
700 | 1 | |a Singh, Gagandeep |e verfasserin |4 aut | |
700 | 1 | |a Brustolin, Marco |e verfasserin |4 aut | |
700 | 1 | |a Cantero, Guillermo |e verfasserin |4 aut | |
700 | 1 | |a Roca, Núria |e verfasserin |4 aut | |
700 | 1 | |a Pérez, Mònica |e verfasserin |4 aut | |
700 | 1 | |a Bustos-Morán, Eugenio |e verfasserin |4 aut | |
700 | 1 | |a White, Kris |e verfasserin |4 aut | |
700 | 1 | |a Schotsaert, Michael |e verfasserin |4 aut | |
700 | 1 | |a García-Sastre, Adolfo |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Journal of immunology (Baltimore, Md. : 1950) |d 1945 |g 212(2024), 8 vom: 15. Apr., Seite 1307-1318 |w (DE-627)NLM000018554 |x 1550-6606 |7 nnns |
773 | 1 | 8 | |g volume:212 |g year:2024 |g number:8 |g day:15 |g month:04 |g pages:1307-1318 |
856 | 4 | 0 | |u http://dx.doi.org/10.4049/jimmunol.2300426 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 212 |j 2024 |e 8 |b 15 |c 04 |h 1307-1318 |