Antagonism of new Flavonoids from Sophorica japonica on IL-3-induced eosinophil activation / 천식및알레르기

ABSTRACT

BACKGROUND: Even though allergic disease is an inflammatory disease, main inflammatory cells and cytokines involved in this process are different from those in other inflammatory diseases. New therapeutic targets on allergic inflammation include eosinophils, mast cells, T lymphocytes and their cytokines activating those cells, so new antagonists acting on them are under many investigations. We extracted four iso-flavonoids from Sophorica japonica such as Sophi, Orbol, Luten, and Genistein which has been known PTK antagonist. We documented the three iso-flavonoids, except Genistein, had an antagonism on IL-5 using in vitro IL -5-induced eosinophil activation model and also in allergic mouse model sensitized by OA (ovualbumin). One of our data from mouse model, which was those three compounds blocked early allergic response near completely, suggested they might have an antagonism on IL-3, the major cytokine activating mast cell and basophils which control early allergic response mainly. OBJECTIVE: From the above results, we tried to find antagonistic effects of the compounds on IL-3 using IL-3 - induced eosinophil activation model in vitro. METHODS: LTC4 by RIA and degree of degranulation by light and electron microscopic examination were used as the activation markers of eosinophils. RESULTS: Among the compounds, Sophi was the most potent antagonist on IL-3 which induced LTC4 release and even on degranulation, and Orbol and Luten also had antagonism on them, but Genistein, an antagonist of PTK didn't show any antagonistic effects. CONCLUSION: We conclude that those three iso-flavonoids were IL-3 antagonists, and its mechanism might not be through PTK signaling.