title: Anacardic acid, a histone acetyltransferase inhibitor, modulates LPS-induced IL-8 expression in a human alveolar epithelial cell line A549.
abstract: OBJECTIVE
  The histone acetylation processes, which are believed to play a critical role in the regulation of many inflammatory genes, are reversible and regulated by histone acetyltransferases (HATs), which promote acetylation, and histone deacetylases (HDACs), which promote deacetylation. We studied the effects of lipopolysaccharide (LPS) on histone acetylation and its role in the regulation of interleukin (IL)-8 expression.
  
  
  METHODS
  A human alveolar epithelial cell line A549 was used in vitro.
  
  
  METHODS
  Histone H4 acetylation at the IL-8 promoter region was assessed by a chromatin immunoprecipitation (ChIP) assay. The expression and production of IL-8 were evaluated by quantitative polymerase chain reaction and specific immunoassay. Effects of a HDAC inhibitor, trichostatin A (TSA), and a HAT inhibitor, anacardic acid, were assessed.
  
  
  RESULTS
  Escherichia coli-derived LPS showed a dose- and time-dependent stimulatory effect on IL-8 protein production and mRNA expression in A549 cells in vitro. LPS showed a significant stimulatory effect on histone H4 acetylation at the IL-8 promoter region by ChIP assay. Pretreatment with TSA showed a dose-dependent stimulatory effect on IL-8 release from A549 cells as compared to LPS alone. Conversely, pretreatment with anacardic acid inhibited IL-8 production and expression in A549 cells.
  
  
  CONCLUSIONS
  These data suggest that LPS-mediated proinflammatory responses in the lungs might be modulated via changing chromatin remodeling by HAT inhibition.
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yasutake
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Higaki
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Masuo
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.affiliation: Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, 181-8611, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Goto