In vitro anti-allergic activity of the fungal metabolite pyridovericin.

ABSTRACT

Mast cells play a critical role during the development of an allergic response. Upon activation by an antigen and IgE, via FcεRI receptors, mast cells release histamine and other mediators that initiate and propagate immediate hypersensitivity reactions. Mast cells also secrete cytokines that regulate the immune responses. In this way, inhibitors of mast cell activity could work as promising therapeutics for allergic disorders. In the present work, we investigated the capacity of pyridovericin, a natural product isolated from the entomopathogenic fungus Beauveria bassiana, to inhibit mast cell degranulation and cytokine secretion. It was found that pyridovericin strongly decreased the release of ß-hexosaminidase, a marker for mast cell degranulation, when mast cells were stimulated by both FcεRI-dependent and independent pathways. In addition, pyridovericin strongly abrogated secretion of interleukin-4. Pyridovericin-mediated suppression of stimulated increase in intracellular Ca(2+) levels, a crucial signal for mounting of both degranulation and cytokine production responses, was ascribed as one of the inhibition targets of pyridovericin. Those initial studies identify pyridovericin as a potential new candidate for the development of new anti-allergic drugs.