Introduction: Combining anti-viral and anti-inflammatory effects in a single drug may be beneficial in treating COVID-19. We hypothesized that the TLR7 agonist imiquimod (imq) may exert these actions in human bronchial epithelial cells (HBECs), which are targets in SARS-CoV-2 mediated lung injury. Methods: Using primary HBECs from asthmatic donors (N=18), we explored actions of imq related to airway viral resistance and tolerance. HBECs were treated with imq alone or in combination with the viral mimic poly (I:C) or the SARS-CoV-2 spike protein 1 (SP1). Anti-viral and pro-inflammatory mediators were analyzed by Luminex, RT-qPCR and mRNA gene pathway analysis. Results: imq treatment alone induced IFN-ß and CCL5 (p<0.05) mRNA and reduced transcription of IL-1ß (p<0.01) at 24h. In SP1 or poly (I:C) stimulated HBECs, treatment with imq augmented IFN-ß mRNA expression by a 2-fold, respectively (p<0.05). Imq in combination with poly (I:C) decreased protein release of IL-8, CCL5, IL-1ß and IL-6 (p<0.05). Furthermore, gene pathway analysis revealed that imq enriched poly(I:C)-induced IFN signaling, IL-20 family signaling (epithelial repair), antigen presentation and cytokine signaling. Enriched cytokine signaling genes included negative regulators such as IKBKG and SIGIRR. Conclusion: imq exerts distinct anti-viral resistance effects in HBECs by increasing anti-viral signaling and improves viral infection tolerance by diminishing epithelial cytokines potentially involved in severe COVID-19. Our findings highlight a possibility of developing dual action drugs suitable for anti-SARS-CoV-2 treatment.
|Status||Published - 2021|
|Evenemang||European Respiratory Society (ERS) congress 2021 - |
Varaktighet: 2021 sep 5 → …
|Konferens||European Respiratory Society (ERS) congress 2021|
|Period||2021/09/05 → …|
- Lungmedicin och allergi