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Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation.

Publication ,  Journal Article
Kelleher, ZT; Sha, Y; Foster, MW; Foster, WM; Forrester, MT; Marshall, HE
Published in: J Biol Chem
January 31, 2014

S-nitrosylation of nuclear factor κB (NF-κB) on the p65 subunit of the p50/p65 heterodimer inhibits NF-κB DNA binding activity. We have recently shown that p65 is constitutively S-nitrosylated in the lung and that LPS-induced injury elicits a decrease in SNO-p65 levels concomitant with NF-κB activation in the respiratory epithelium and initiation of the inflammatory response. Here, we demonstrate that TNFα-mediated activation of NF-κB in the respiratory epithelium similarly induces p65 denitrosylation. This process is mediated by the denitrosylase thioredoxin (Trx), which becomes activated upon cytokine-induced degradation of thioredoxin-interacting protein (Txnip). Similarly, inhibition of Trx activity in the lung attenuates LPS-induced SNO-p65 denitrosylation, NF-κB activation, and airway inflammation, supporting a pathophysiological role for this mechanism in lung injury. These data thus link stimulus-coupled activation of NF-κB to a specific, protein-targeted denitrosylation mechanism and further highlight the importance of S-nitrosylation in the regulation of the immune response.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 31, 2014

Volume

289

Issue

5

Start / End Page

3066 / 3072

Location

United States

Related Subject Headings

  • Transcription Factor RelA
  • Thioredoxins
  • Signal Transduction
  • Respiratory Mucosa
  • Reactive Nitrogen Species
  • Nitric Oxide
  • NF-kappa B p50 Subunit
  • Mice, Inbred C57BL
  • Mice
  • Male
 

Citation

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Kelleher, Z. T., Sha, Y., Foster, M. W., Foster, W. M., Forrester, M. T., & Marshall, H. E. (2014). Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation. J Biol Chem, 289(5), 3066–3072. https://doi.org/10.1074/jbc.M113.503938
Kelleher, Zachary T., Yonggang Sha, Matthew W. Foster, W Michael Foster, Michael T. Forrester, and Harvey E. Marshall. “Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation.J Biol Chem 289, no. 5 (January 31, 2014): 3066–72. https://doi.org/10.1074/jbc.M113.503938.
Kelleher ZT, Sha Y, Foster MW, Foster WM, Forrester MT, Marshall HE. Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation. J Biol Chem. 2014 Jan 31;289(5):3066–72.
Kelleher, Zachary T., et al. “Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation.J Biol Chem, vol. 289, no. 5, Jan. 2014, pp. 3066–72. Pubmed, doi:10.1074/jbc.M113.503938.
Kelleher ZT, Sha Y, Foster MW, Foster WM, Forrester MT, Marshall HE. Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation. J Biol Chem. 2014 Jan 31;289(5):3066–3072.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

January 31, 2014

Volume

289

Issue

5

Start / End Page

3066 / 3072

Location

United States

Related Subject Headings

  • Transcription Factor RelA
  • Thioredoxins
  • Signal Transduction
  • Respiratory Mucosa
  • Reactive Nitrogen Species
  • Nitric Oxide
  • NF-kappa B p50 Subunit
  • Mice, Inbred C57BL
  • Mice
  • Male