Novel Method for Selecting Immunosuppressive Histone Deacetylase (HDAC) Inhibitors with Minimal Thrombocytopenia

• Published in: Biological & pharmaceutical bulletin Vol. 31; no. 2; pp. 305 - 308
• Main Authors: Matsuoka, Hideaki, Fujimura, Takao, Unami, Akira, Yamada, Toshiko, Noto, Takahisa, Takata, Yoko, Yoshizawa, Katsuhiko, Mori, Hiroaki, Aramori, Ichiro, Mutoh, Seitaro
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.02.2008; Japan Science and Technology Agency
• Subjects: Animals; Cell Survival - drug effects; Drug Evaluation, Preclinical; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacology; GATA binding protein-1; GATA1 Transcription Factor - genetics; Genes, Reporter - drug effects; Heart Transplantation - immunology; histone deacetylase inhibitor; Histone Deacetylase Inhibitors; Humans; immunosuppression; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - pharmacology; interleukin-2; Interleukin-2 - genetics; Jurkat Cells; Male; Plasmids - genetics; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; Structure-Activity Relationship; Tetrazolium Salts; Thiazoles; thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - chemically induced; Transplantation, Heterotopic - immunology

Histone deacetylase (HDAC) inhibitors repress interleukin-2 (IL-2) gene expression in T cells and possess immunosuppressive activity in vivo. In addition to its immunosuppressive activity, HDAC inhibitors block GATA binding protein-1 (GATA-1) gene expression in megakaryocytes and elicit thrombocytop...