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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. [ABSTRACT FROM AUTHOR]

Background: Herbal remedies predate written history and continue to be used more frequently than conventional pharmaceutical medications. Thymoquinone (TQ) is a traditional herb that has been used for its anti-inflammatory, antioxidant, and chemopreventive effects. Montelukast is a conventional medication used to treat allergic rhinitis and asthma. The aim of this research was to evaluate the effects of TQ and montelukast on human respiratory epithelium specifically addressing effects on cilia beat frequency (CBF). Methods: Well-differentiated human sinonasal epithelial cultures, grown at an air-liquid interface were treated with varying concentrations of TQ and montelukast. Changes in CBF were determined using the Sissons-Ammons Video Analysis system. Results: When applied to the basolateral surface, TQ showed a statistically significant dose-dependent increase in CBF with maximal stimulation at 30 minutes. Effects of montelukast on CBF showed both time and dose dependence with maximal stimulatory effect measured at 6 hours. Conclusion: The results of our study indicate that TQ and montelukast have dose-dependent effects on CBF, extending their mechanism of action in respiratory diseases. [ABSTRACT FROM AUTHOR]