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Nuclear Factor-κB and TNF-α Mediate Gastric Ulceration Induced by Phorbol Myristate Acetate

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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.

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Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan

    Tetsu Takeuchi, Lin Wang, Keita Uehara, Misa Mizumori, Hiroshi Kishikawa, Hajime Higuchi, Masayuki Adachi, Hiromasa Nakamizo & Hiromasa Ishii

  2. Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan

    Soichiro Miura & Ryota Hokari

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  1. Tetsu Takeuchi
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  2. Soichiro Miura
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  3. Lin Wang
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Takeuchi, T., Miura, S., Wang, L. et al. Nuclear Factor-κB and TNF-α Mediate Gastric Ulceration Induced by Phorbol Myristate Acetate. Dig Dis Sci 47, 2070–2078 (2002). https://doi.org/10.1023/A:1019633114854

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