We investigated the role of
febuxostat through in vitro cell and in vivo animal experiments. Human nasal epithelial cells (hNECs) were cultured with
histamine as an in vitro model. To establish the AR animal model, rats were exposed to
ovalbumin. Rats were randomly grouped into control, model, 7.5 mg/kg
febuxostat, and 15 mg/kg
febuxostat groups.
Results: In the in vitro study, we found significantly increased release of
lactate dehydrogenase, elevated production of inflammatory factors and
chemokines, and upregulated CAMs in
histamine-treated hNECs. However, these results were significantly reversed for the 10 and 20 μM
febuxostat treatments. The enhanced adhesion between hNECs and monocytes induced by
histamine was dramatically repressed by
febuxostat. In the vivo experiments, we observed that
febuxostat ameliorated the increased
sneezing times, the number of nose scratching episodes, and elevated HE pathological scores as well as alleviated the
inflammation in nasal mucous tissues of AR mice. We found that KLF6, which was downregulated in
histamine-treated hNECs, was significantly upregulated by
febuxostat. The inhibitory effects of
febuxostat on the expression levels of CAMs and adhesion between
histamine-treated hNECs and monocytes were significantly abolished by the knockdown of KLF6.
Conclusion: