Abstract
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 language | English (US) |
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Pages (from-to) | G1405-G1412 |
Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 281 |
Issue number | 6 44-6 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Cytokines
- Gastric cells
- Mitogen-activated protein kinase
- Protein kinase C
- Signaling
- Tumor necrosis factor
ASJC Scopus subject areas
- Physiology
- Hepatology
- Gastroenterology
- Physiology (medical)