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.
Tachibana
H
H
Graduate School of Bioresources and Bioenvironmental Science, Kyushu University, Hakozaki 6-10-1, Higashi-ku, Fukuoka, 812-8581, Japan. tatibana@agr.kyushu-u.ac.jp
Kubo
T
T
Miyase
T
T
Tanino
S
S
Yoshimoto
M
M
Sano
M
M
Yamamoto-Maeda
M
M
Yamada
K
K
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology*; D002051:Burkitt Lymphoma; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D018515:Plant Leaves; D013662:Tea; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D013662:Tea; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin