Identification of an inhibitor for interleukin 4-induced epsilon germline transcription and antigen-specific IgE production in vivo.

IgE plays a key role in the pathogenesis of allergic disease. Interleukin (IL) 4 is a potent and critical stimulator of immunoglobulin class switching from IgM to IgE in B cells. IL-4 induces the expression of epsilon germline transcript (epsilonGT), which is critical to initiate IgE production. While searching for molecules that inhibit epsilonGT expression induced by IL-4, we found that polyphenol strictinin, which was isolated from tea leaves, was able to inhibit the IL-4-induced epsilonGT expression in the human B cell line DND39. Strictinin also acted on human peripheral blood mononuclear cells obtained from healthy donors to inhibit IL-4-induced epsilonGT expression. Strictinin demonstrated similar inhibitory activity in peripheral blood mononuclear cells obtained from atopic donors. Interestingly, strictinin decreased ovalbumin-induced IgE production in mice, whereas the production of IgG and IgM was not affected. Furthermore, we found that the IL-4-induced STAT6 tyrosine phosphorylation, which is essential for IL-4-induced epsilonGT expression, was inhibited in DND39 cells upon treatment with strictinin. Taken together, these results suggest that strictinin can inhibit IgE production through the inhibition of IL-4-mediated signaling in B cells.