HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region.
The expression of IL-5 correlated tightly with the maturation and differentiation of eosinophils, and is considered as a cytokine responsible for allergic inflammation. We report here that inhibition of HDAC activity by Trichostatin A (TSA) and sodium butyrate (NaBu), the two specific HDAC inhibitors, resulted in the elevation of both endogenous and exogenous activity of IL-5 promoter. We demonstrated that both the mRNA expression and protein production of IL-5 were stimulated by TSA and NaBu treatments. ChIP assays showed that treatments of TSA and NaBu caused hyperacetylation of histones H3 and H4 on IL-5 promoter in Jurkat cells, which consequently promoted the exogenous luciferase activity driven by this promoter. Moreover, site-directed mutagenesis studies showed that the binding sites for transcription factors NFAT, GATA3 and YY1 on IL-5 promoter were critical for the effects of TSA and NaBu, suggesting that the transcriptional activation of IL-5 gene by these inhibitors was achieved by affecting HDAC function on IL-5 promoter via transcription factors. These data will contribute to elucidating the unique mechanism of IL-5 transcriptional control and to the therapy of allergic disorders related to IL-5.
Han
Songyan
S
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130022, China.
Lu
Jun
J
Zhang
Yu
Y
Cheng
Cao
C
Li
Lin
L
Han
Liping
L
Huang
Baiqu
B
D000107:Acetylation / Q000187:drug effects; D020148:Butyric Acid / Q000494:pharmacology*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D015848:Interleukin-5 / Q000235:genetics* / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C508599:IL5 protein, human; D015848:Interleukin-5; D020148:Butyric Acid; C012589:trichostatin A; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate