Differential effects of histone deacetylase inhibitors on interleukin-18 gene expression in myeloid cells.
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.
Koyama
Noriko
N
Department of Hematology, Johann Wolfgang Goethe University, Frankfurt, 60590, Germany. Koyama@em.uni-frankfurt.de
Koschmieder
Steffen
S
Tyagi
Sandhya
S
Nürnberger
Heike
H
Wagner
Sandra
S
Böcker
U
U
Hoelzer
Dieter
D
Gerhard Ottmann
Oliver
O
Kalina
Uwe
U
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
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