Benzyl isothiocyanate attenuates the hydrogen peroxide-induced interleukin-13 expression through glutathione S-transferase P induction in T lymphocytic leukemia cells

J Biochem Mol Toxicol. 2018 Jun;32(6):e22054. doi: 10.1002/jbt.22054. Epub 2018 Apr 18.

Abstract

We investigated the effect of benzyl isothiocyanate (BITC) on the hydrogen peroxide-induced gene expression of a T-helper-2 cytokine, interleukin (IL)-13, in T lymphocytic leukemia Jurkat cells. The 24-h pretreatment of BITC significantly inhibited the IL-13 expression enhanced by hydrogen peroxide. Although the BITC pretreatment did not change the enhanced level of the phosphorylated c-Jun N-terminal kinase (JNK), it significantly inhibited the nuclear translocation of c-Jun induced by hydrogen peroxide. BITC also increased the protein expression of glutathione S-transferase (GST) isozymes, GSTP1/2, as well as the total GST activity. A GSTP1/2-specific inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly counteracted the inhibitory effect of BITC on the hydrogen peroxide-enhanced IL-13 upregulation as well as the c-Jun nuclear translocation. Taken together, these results suggested that BITC inhibits the oxidative stress-mediated IL-13 mRNA expression, possibly through interference of the c-Jun phosphorylation by GSTP.

Keywords: benzyl isothiocyanate; c-Jun; glutathione S-transferase; hydrogen peroxide; interleukin 13.

MeSH terms

  • Cell Nucleus / enzymology
  • Enzyme Inhibitors / pharmacology
  • Glutathione Transferase / antagonists & inhibitors
  • Glutathione Transferase / biosynthesis*
  • Humans
  • Hydrogen Peroxide / toxicity*
  • Interleukin-13 / genetics*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Isothiocyanates / toxicity*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Jurkat Cells
  • Oxadiazoles / pharmacology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics
  • Phosphorylation
  • Protein Transport
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol
  • Enzyme Inhibitors
  • Interleukin-13
  • Isoenzymes
  • Isothiocyanates
  • Oxadiazoles
  • RNA, Messenger
  • benzyl isothiocyanate
  • Hydrogen Peroxide
  • Glutathione Transferase
  • JNK Mitogen-Activated Protein Kinases