TNF-α and interleukin 1 activate gastrin gene expression via MAPK- and PKC-dependent mechanisms

T. Suzuki, E. Grand, C. Bowman, J. L. Merchant, A. Todisco, L. Wang, J. Del Valle

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Helicobacter pylori and proinflammatory cytokines have a direct stimulatory effect on gastrin release from isolated G cells, but little is known about the mechanism by which these factors regulate gastrin gene expression. We explored whether tumor necrosis factor (TNF)-α and interleukin (IL)-1 directly regulate gastrin gene expression and, if so, by what mechanism. TNF-α and IL-1 significantly increased gastrin mRNA in canine G cells to 181 ± 18% and 187 ± 28% of control, respectively, after 24 h of treatment. TNF-α and IL-1 stimulated gastrin promoter activity to a maximal level of 285 ± 12% and 415 ± 26% of control. PD-98059 (a mitogen-activated protein kinase kinase inhibitor), SB-202190 (a p38 kinase inhibitor), and GF-109203 (a protein kinase C inhibitor) inhibited the stimulatory action of both cytokines on the gastrin promoter. In conclusion, both cytokines can directly regulate gastrin gene expression via a mitogen-activated protein kinase- and protein kinase C-dependent mechanism. These data suggest that TNF-α and IL-1 may play a direct role in Helicobacter pylori-induced hypergastrinemia.

Original languageEnglish (US)
Pages (from-to)G1405-G1412
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number6 44-6
StatePublished - 2001
Externally publishedYes


  • Cytokines
  • Gastric cells
  • Mitogen-activated protein kinase
  • Protein kinase C
  • Signaling
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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