Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells.

Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells. Research Abstract Details 

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Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells. Abstract Text:

Hideaki Matsuoka,Takao Fujimura,Hiroaki Mori,Ichiro Aramori,Seitaro Mutoh,Hideaki Matsuoka,Takao Fujimura,Hiroaki Mori,Ichiro Aramori,Seitaro Mutoh,

Interleukin (IL)-2 is an essential cytokine in T cell proliferation and homeostasis. The importance of IL-2 down-regulation in preventing acute rejection in organ transplantation and the development of autoimmune diseases has been demonstrated by the therapeutic usefulness of the widely used immunosuppressants cyclosporine A and FK506. Recently, a histone deacetylase (HDAC) inhibitor, FR235222, has been shown to inhibit IL-2 gene expression and to possess immunosuppressive activity in vivo. To elucidate the inhibitory mechanism of FR235222 in IL-2 gene expression, we performed Affymetrix GeneChip analysis of activated Jurkat cells treated with or without FR235222. Here, we show that many NF-kappaB-regulated genes are transcriptionally down-regulated by FR235222 in activated Jurkat cells. Further, luciferase reporter assays revealed that FR235222 selectively inhibits NF-kappaB activity without impairing NF-AT or AP-1 at the concentrations at which it potently inhibits IL-2 promoter activation. These results indicate that FR235222 inhibits IL-2 gene expression via a different mechanism to CsA and FK506, and that FR235222 has the ability to inhibit NF-kappaB activity, which may be partly related to the potent inhibition of IL-2 gene expression by FR235222. Our findings may help our understanding of the molecular mechanism of the inhibition of IL-2 gene expression by HDAC inhibitors and provide insight into the development of more effective and safer new immunosuppressants.

Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells. Publishing Authors By Initials

H Matsuoka,T Fujimura,H Mori,I Aramori,S Mutoh,H Matsuoka,T Fujimura,H Mori,I Aramori,S Mutoh,

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Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: International immunopharmacology

VOLUME: 7

Page Numbers: 1422-32

Journal Abbreviation: Int. Immunopharmacol.

ISSN: 1567-5769

DAY: 17

MONTH: 07

YEAR: 2007

Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Mechanism of HDAC inhibitor FR235222-mediated IL-2 transcriptional repression in Jurkat cells.

AFFILIATION: Pharmacology Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. hideaki.matsuoka@jp.astellas.com

Country: Netherlands

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MEDLINETA: Int Immunopharmacol

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