title: Differential effects of histone deacetylase inhibitors on interleukin-18 gene expression in myeloid cells.
abstract: Histone deacetyrase (HDAC) inhibitors induce growth arrest and differentiation of leukemia cell lines and tumor cells derived from a large variety of human tissues. Here we showed that HDAC inhibitors sodium butyrate, TSA, and valproate regulated the expression of Interleukin-18 (IL-18), a cytokine with antitumor and proinflammatory properties, in human acute myeloid leukemia cell lines U937 and HEL. Sodium butyrate increased expression of IL-18 protein and mRNA and activated 1357bp IL-18 gene promoter construct. IL-18 mRNA level was up-regulated by TSA or valproate, which also activated IL-18 full-length promoter. While sodium butyrate or TSA stimulated the 108-bp IL-18 minimal promoter, valproate failed to activate it, indicating that valproate may use a distinct mechanism from sodium butyrate and TSA to activate IL-18 gene expression.
authors.affiliation: Department of Hematology, Johann Wolfgang Goethe University, Frankfurt, 60590, Germany. Koyama@em.uni-frankfurt.de
authors.forename: Noriko
authors.initials: N
authors.lastname: Koyama
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.forename: Sandhya
authors.initials: S
authors.lastname: Tyagi
authors.forename: Heike
authors.initials: H
authors.lastname: Nürnberger
authors.forename: Sandra
authors.initials: S
authors.lastname: Wagner
authors.forename: U
authors.initials: U
authors.lastname: Böcker
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Oliver
authors.initials: O
authors.lastname: Gerhard Ottmann
authors.forename: Uwe
authors.initials: U
authors.lastname: Kalina
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020298:U937 Cells; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D002087:Butyrates; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D020382:Interleukin-18; D012333:RNA, Messenger; C012589:trichostatin A; D014635:Valproic Acid