Increased IL-2 production in T cells by xanthohumol through enhanced NF-AT and AP-1 activity.
Xanthohumol (XN) is a major chalcone found in hop, which is used to add bitterness and flavor to beer. In this study, we investigated the effects of XN on the production of interlukin-2 (IL-2), a potent T cell growth factor. Treatment with XN significantly increased IL-2 production in mouse EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) in a dose-dependent manner. To further characterize its regulatory mechanism of XN on increased IL-2 production, the effects of XN on IL-2 promoter activity and the activity of several transcription factors modulating IL-2 expression were analyzed. XN enhanced activity of the IL-2 promoter, which contains distal and proximal regulatory elements in PMA/Io-activated EL-4 T cells. Furthermore, the activity of NF-AT and AP-1 was enhanced but NF-kappaB activity was not influenced by XN in PMA/Io-activated EL-4 T cells. These results suggest that XN increased IL-2 production at the transcriptional levels via the up-regulation of NF-AT and AP-1 in PMA/Io-activated EL-4 T cells.
Choi
Jin Myung
JM
College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kim
Hyun Jung
HJ
Lee
Kwang Youl
KY
Choi
Hyun Jin
HJ
Lee
Ik-Soo
IS
Kang
Bok Yun
BY
D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids; D005786:Gene Expression Regulation / Q000187:drug effects; D007202:Indicators and Reagents; D007376:Interleukin-2 / Q000096:biosynthesis*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011427:Propiophenones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection
D005419:Flavonoids; D007202:Indicators and Reagents; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011427:Propiophenones; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D007770:L-Lactate Dehydrogenase; D008156:Luciferases; C104536:xanthohumol