RESUMEN
Asthma is a common chronic inflammatory airway disease. Recent studies have reported that interleukin (IL)33 is a potential link between the airway epithelium and Th2type inflammatory responses, which are closely related to the progression of asthma. The IL33 receptor, ST2, is highly expressed in group 2 innate lymphoid cells (ILC2s), Th2 cells, mast cells, eosinophils and natural killer (NK) cells. Cnidii Fructus is a Chinese herb with a long history of use in the treatment of asthma in China. Osthole is one of the major components of Cnidii Fructus. The present study examined the antiasthmatic effects of osthole in mice and aimed to elucidate the underlying mechanisms involving the IL33/ST2 pathway. BALB/c mice were sensitized and challenged with ovalbumin and then treated with an intraperitoneal injection of osthole (25 and 50 mg/kg). Subsequently, the airway hyperresponsiveness (AHR) and inflammation of the lungs were evaluated. The amounts of IL4, IL5, IL13, interferon (IFN)γ and IL33 in the bronchoalveolar lavage fluid (BALF) were measured by Luminex assay and their mRNA levels in the lungs were measured by reverse transcriptionquantitative PCR. The histopathology of the lungs was performed with H&E, PAS and Masson's staining. The expression of ST2 in the lungs was evaluated by immunohistochemistry. The data demonstrated that osthole markedly reduced AHR and decreased the number of eosinophils and lymphocytes in BALF. It was also observed that osthole significantly inhibited the release of Th2type cytokines (IL4, IL5 and IL13) and upregulated the IFNγ level in BALF. Moreover, osthole significantly attenuated the IL33 and ST2 expression in the lungs of asthmatic mice. On the whole, osthole attenuated ovalbumininduced lung inflammation through the inhibition of IL33/ST2 signaling in an asthmatic mouse model. These results suggest that osthole is a promising target for the development of an asthma medication.