| Title | Interleukin-1beta Promotes Gastric Atrophy Through Suppression of Sonic Hedgehog. | | Author(s) | Waghray M, Zavros Y, Saqui-Salces M, El-Zaatari M, Alamelumangapuram CB, Todisco A, Eaton KA, Merchant JL | | Institution | Department of Internal Medicine, University of Michigan, 109 Zina Pitcher Place, BSRB 2051, Ann Arbor, MI 48109-2200, USA. | | Source | Gastroenterology 2009 Oct 30. | | Abstract | BACKGROUND & AIMS:: In both human subjects and rodent models, Helicobacter infection leads to a decrease in Shh expression in the stomach. Sonic Hedgehog (Shh) is highly expressed in the gastric corpus and its loss correlates with gastric atrophy. Therefore, we tested the hypothesis that proinflammatory cytokines induce gastric atrophy by inhibiting Shh expression.
METHODS:: Shh-LacZ reporter mice were infected with H. felis for 3 and 8 weeks. Changes in Shh expression were monitored using beta-galactosidase staining and immunohistochemistry. Gastric acidity was measured after infection and IL-1beta was quantified by qRT-PCR. Mice were injected with either IL-1beta or omeprazole prior to measuring Shh mRNA expression and acid secretion. Organ cultures of gastric glands from wild type or IL-1R1 null mice were treated with IL-1beta then Shh expression was measured using qRT-PCR. Primary canine parietal or mucous cells were treated with IL-1beta. Shh protein was determined by immunoblot analysis. Changes in intracellular calcium were measured by Fura-2.
RESULTS:: All major cell lineages of the corpus including surface pit, mucous neck, zymogenic and parietal cells expressed Shh. Helicobacter infection reduced gastric acidity and inhibited Shh expression in parietal cells by 3 weeks. IL-1beta produced during Helicobacter infection inhibited gastric acid, intracellular calcium and Shh expression through the IL-1 receptor. Suppression of parietal cell Shh expression by IL-1beta and omeprazole was additive. IL-1beta did not suppress Shh expression in primary gastric mucous cells.
CONCLUSION:: IL-1beta suppresses Shh gene expression in parietal cells by inhibiting acid secretion and subsequently the release of intracellular calcium. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19883649 |
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