Akt activator SC79 stimulates antibacterial nitric oxide generation in human nasal epithelial cells in vitro.

Autor: Lee RJ; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Adappa ND; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Palmer JN; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: International forum of allergy & rhinology [Int Forum Allergy Rhinol] 2024 Jul; Vol. 14 (7), pp. 1147-1162. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1002/alr.23318
Abstrakt: Background: The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small-molecule Akt activator SC79 induces nasal cell NO production and suppresses IL-8 via the transcription factor Nrf-2. We hypothesized that SC79 NO production may additionally have antibacterial effects.
Methods: NO production was measured using fluorescent dye DAF-FM. We tested effects of SC79 during co-culture of Pseudomonas aeruginosa with primary nasal epithelial cells, using CFU counting and live-dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79-induced NO production and tested dependence on Akt.
Results: SC79 induced dose-dependent, Akt-dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killed P. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h.
Conclusions: Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small-molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies.
(© 2024 ARS‐AAOA, LLC.)
Databáze: MEDLINE
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