Nuclear factor-κB and TNF-α mediate gastric ulceration induced by phorbol myristate acetate

Tetsu Takeuchi, Soichiro Miura, Lin Wang, Keita Uehara, Misa Mizumori, Hiroshi Kishikawa, Ryota Hokari, Hajime Higuchi, Masayuki Adachi, Hiromasa Nakamizo, Hiromasa Ishii

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16 Citations (Scopus)

Abstract

Phorbol esters induce inflammation in rodents by activating protein kinase C. We determined whether nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) play role in the formation of gastric ulcer induced by phorbol-12-myristate-13-acetate (PMA) in rats. Subserosally injected PMA dose-dependently induced gastric mucosal ulcer. Activation of NF-κB in the gastric mucosa corresponding to the PMA injection sites was observed before the ulcers became obvious as assessed by an in situ fluorescence DNA binding assay and electrophoretic mobility shift assay. The NF-κB activation and subsequent ulcer formation were significantly inhibited by injection of pyrrolidine dithiocarbamate, proteasome inhibitor (MG132), or NF-κB decoy. Antibody against TNF-α significantly inhibited ulcer formation without attenuating NF-κB activation. These results suggest that both NF-κB activation followed by TNF-α release contribute to tissue damage in PMA-induced gastric ulcer formation.

Original languageEnglish
Pages (from-to)2070-2078
Number of pages9
JournalDigestive Diseases and Sciences
Volume47
Issue number9
DOIs
Publication statusPublished - 2002 Sep 1

Keywords

  • Gastric ulcer
  • Nuclear factor-κB
  • Phorbol ester
  • Protein kinase C
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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    Takeuchi, T., Miura, S., Wang, L., Uehara, K., Mizumori, M., Kishikawa, H., Hokari, R., Higuchi, H., Adachi, M., Nakamizo, H., & Ishii, H. (2002). Nuclear factor-κB and TNF-α mediate gastric ulceration induced by phorbol myristate acetate. Digestive Diseases and Sciences, 47(9), 2070-2078. https://doi.org/10.1023/A:1019633114854