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10.3389/fimmu.2021.743890

http://scihub22266oqcxt.onion/10.3389/fimmu.2021.743890
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suck abstract from ncbi


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pmid34950134      Front+Immunol 2021 ; 12 (ä): 743890
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  • Imiquimod Boosts Interferon Response, and Decreases ACE2 and Pro-Inflammatory Response of Human Bronchial Epithelium in Asthma #MMPMID34950134
  • Nieto-Fontarigo JJ; Tillgren S; Cerps S; Sverrild A; Hvidtfeldt M; Ramu S; Menzel M; Sander AF; Porsbjerg C; Uller L
  • Front Immunol 2021[]; 12 (ä): 743890 PMID34950134show ga
  • 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(I:C), 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(I:C) stimulation. Imiquimod also reduced poly(I:C)-induced pro-inflammatory cytokines including IL-1beta, IL-6, IL-8, and IL-33. Furthermore, imiquimod increased IFN-beta expression, an effect potentiated in presence of poly(I:C) 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(I:C). 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-beta 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.
  • |*Asthma[MESH]
  • |*COVID-19[MESH]
  • |Adjuvants, Immunologic/pharmacology[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Angiotensin-Converting Enzyme 2/*metabolism[MESH]
  • |Bronchi/drug effects/immunology/virology[MESH]
  • |Cells, Cultured[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Imiquimod/*pharmacology[MESH]
  • |Interferon-beta/*drug effects/immunology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Respiratory Mucosa/*drug effects/metabolism/virology[MESH]


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