Imiquimod Boosts Interferon Response, and Decreases ACE2 and Pro-Inflammatory Response of Human Bronchial Epithelium in Asthma.
Front Immunol
; 12: 743890, 2021.
Article
em En
| MEDLINE
| ID: mdl-34950134
ABSTRACT
Background:
Both anti-viral and anti-inflammatory bronchial effects are warranted to treat viral infections in asthma. We sought to investigate if imiquimod, a TLR7 agonist, exhibits such dual actions in ex vivo cultured human bronchial epithelial cells (HBECs), targets for SARS-CoV-2 infectivity.Objective:
To investigate bronchial epithelial effects of imiquimod of potential importance for anti-viral treatment in asthmatic patients.Methods:
Effects of imiquimod alone were examined in HBECs from healthy (N=4) and asthmatic (N=18) donors. Mimicking SARS-CoV-2 infection, HBECs were stimulated with poly(IC), a dsRNA analogue, or SARS-CoV-2 spike-protein 1 (SP1; receptor binding) with and without imiquimod treatment. Expression of SARS-CoV-2 receptor (ACE2), pro-inflammatory and anti-viral cytokines were analyzed by RT-qPCR, multiplex ELISA, western blot, and Nanostring and proteomic analyses.Results:
Imiquimod reduced ACE2 expression at baseline and after poly(IC) stimulation. Imiquimod also reduced poly(IC)-induced pro-inflammatory cytokines including IL-1ß, IL-6, IL-8, and IL-33. Furthermore, imiquimod increased IFN-ß expression, an effect potentiated in presence of poly(IC) or SP1. Multiplex mRNA analysis verified enrichment in type-I IFN signaling concomitant with suppression of cytokine signaling pathways induced by imiquimod in presence of poly(IC). Exploratory proteomic analyses revealed potentially protective effects of imiquimod on infections.Conclusion:
Imiquimod triggers viral resistance mechanisms in HBECs by decreasing ACE2 and increasing IFN-ß expression. Additionally, imiquimod improves viral infection tolerance by reducing viral stimulus-induced epithelial cytokines involved in severe COVID-19 infection. Our imiquimod data highlight feasibility of producing pluripotent drugs potentially suited for anti-viral treatment in asthmatic subjects.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Asma
/
Interferon beta
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Mucosa Respiratória
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Imiquimode
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Enzima de Conversão de Angiotensina 2
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COVID-19
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article