Serum Amyloid P inhibits single stranded RNA-induced lung inflammation, lung damage, and cytokine storm in mice.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
21
08
2020
accepted:
09
01
2021
entrez:
22
1
2021
pubmed:
23
1
2021
medline:
3
2
2021
Statut:
epublish
Résumé
SARS-CoV-2 is a single stranded RNA (ssRNA) virus and contains GU-rich sequences distributed abundantly in the genome. In COVID-19, the infection and immune hyperactivation causes accumulation of inflammatory immune cells, blood clots, and protein aggregates in lung fluid, increased lung alveolar wall thickness, and upregulation of serum cytokine levels. A serum protein called serum amyloid P (SAP) has a calming effect on the innate immune system and shows efficacy as a therapeutic for fibrosis in animal models and clinical trials. Here we show that aspiration of the GU-rich ssRNA oligonucleotide ORN06 into mouse lungs induces all of the above COVID-19-like symptoms. Men tend to have more severe COVID-19 symptoms than women, and in the aspirated ORN06 model, male mice tended to have more severe symptoms than female mice. Intraperitoneal injections of SAP starting from day 1 post ORN06 aspiration attenuated the ORN06-induced increase in the number of inflammatory cells and formation of clot-like aggregates in the mouse lung fluid, reduced ORN06-increased alveolar wall thickness and accumulation of exudates in the alveolar airspace, and attenuated an ORN06-induced upregulation of the inflammatory cytokines IL-1β, IL-6, IL-12p70, IL-23, and IL-27 in serum. SAP also reduced D-dimer levels in the lung fluid. In human peripheral blood mononuclear cells, SAP attenuated ORN06-induced extracellular accumulation of IL-6. Together, these results suggest that aspiration of ORN06 is a simple model for both COVID-19 as well as cytokine storm in general, and that SAP is a potential therapeutic for diseases with COVID-19-like symptoms and/or a cytokine storm.
Identifiants
pubmed: 33481950
doi: 10.1371/journal.pone.0245924
pii: PONE-D-20-26292
pmc: PMC7822324
doi:
Substances chimiques
Serum Amyloid P-Component
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0245924Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL132919
Pays : United States
Organisme : NIH HHS
ID : GM118355-03S1
Pays : United States
Organisme : NIH HHS
ID : HL 132919
Pays : United States
Commentaires et corrections
Type : UpdateOf
Déclaration de conflit d'intérêts
I have read the journal’s policy and the authors of this manuscript have the following competing interests: Texas A&M University has a patent application on the use of SAP to treat cytokine storm and COVID-19-associated lung inflammation and lung damage. DP, TRK, and RHG are inventors on this patent application. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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