Dexamethasone inhibits phosphorylation of histone H3 at serine 10.
Glucocorticoids are the most effective anti-inflammatory drugs used in the treatment of inflammatory diseases. While phosphorylation of histone H3 at serine 10 (p-Ser10) is one of the histone modifications related to transcription of some inflammation-related genes, the effect of glucocorticoids on p-Ser10 is not established. Here, we investigated the ability of dexamethasone (Dex) to inhibit p-Ser10 expression in response to tumor necrosis factor (TNF-alpha) in the human lung adenocarcinoma cell line A549 and the SV-40-transformed human airway epithelial cell line BEAS-2B. By Western blot analysis in BEAS-2B cells, the expression of p-Ser10 was repressed by pretreatment with Dex, an effect not seen in A549 cells. Flow cytometric analysis at a single-cell level in A549 cells indicated that TNF-alpha treatment caused early induction of p-Ser10 at 15 min, which was inhibited significantly by pretreatment with 10(-5) M Dex. By immunostaining, the p-Ser10 signal appeared as granules in TNF-alpha-treated cells at same sites of phosphorylated RNA polymerase II. In contrast, the signal was scattered in the nuclei of Dex-pretreated cells. These findings suggested that Dex limits airway inflammation by inhibiting p-Ser10 expression and redistributing p-Ser10 away from transcription sites.
Hasegawa
Yasuyuki
Y
Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago, Japan. hasechi@grape.med.tottori-u.ac.jp
Tomita
Katsuyuki
K
Watanabe
Masanari
M
Yamasaki
Akira
A
Sano
Hiroyuki
H
Hitsuda
Yutaka
Y
Shimizu
Eiji
E
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D006657:Histones; D014409:Tumor Necrosis Factor-alpha; D012694:Serine; D003907:Dexamethasone; D012319:RNA Polymerase II