Gastroenterology
Volume 138, Issue 2 , Pages 562-572.e2 , February 2010

Interleukin-1β Promotes Gastric Atrophy Through Suppression of Sonic Hedgehog

  • Meghna Waghray

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Yana Zavros

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Milena Saqui–Salces

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Mohamad El–Zaatari

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • C. Bharath Alamelumangapuram

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan
    • Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan
    • ,
  • Andrea Todisco

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • ,
  • Kathryn A. Eaton

      Affiliations

    • Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan
    • ,
  • Juanita L. Merchant

      Affiliations

    • Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    • Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan
    • Corresponding Author InformationReprint requests Address requests for reprints to: Juanita L. Merchant, MD, PhD, 2051 BSRB, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109-2200. fax: (734) 763-4686

Received 12 March 2009 ,Accepted 22 October 2009.

References 

  1. El-Omar EM, Oien K, El-Nujumi A, et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology. 1997;113:15–24
  2. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789
  3. El-Zimaity HM. Gastric atrophy, diagnosing and staging. World J Gastroenterol. 2006;12:5757–5762
  4. El-Zimaity HM, Ota H, Graham DY, et al. Patterns of gastric atrophy in intestinal type gastric carcinoma. Cancer. 2002;94:1428–1436
  5. Tsukamoto T, Mizoshita T, Tatematsu M. Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization. Gastric Cancer. 2006;9:156–166
  6. Schmidt PH, Lee JR, Joshi V, et al. Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest. 1999;79:639–646
  7. van den Brink GR, Hardwick JC, Nielsen C, et al. Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract. Gut. 2002;51:628–633
  8. van den Brink GR, Hardwick JC, Tytgat GN, et al. Sonic hedgehog regulates gastric gland morphogenesis in man and mouse. Gastroenterology. 2001;121:317–328
  9. Ramalho-Santos M, Melton DA, McMahon AP. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 2000;127:2763–2772
  10. Kim JH, Huang Z, Mo R. Gli3 null mice display glandular overgrowth of the developing stomach. Dev Dyn. 2005;234:984–991
  11. El-Zaatari M, Tobias A, Grabowska AM, et al. De-regulation of the sonic hedgehog pathway in the InsGas mouse model of gastric carcinogenesis. Br J Cancer. 2007;96:1855–1861
  12. Fukaya M, Isohata N, Ohta H, et al. Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer. Gastroenterology. 2006;131:14–29
  13. Minegishi Y, Suzuki H, Arakawa M, et al. Reduced Shh expression in TFF2-overexpressing lesions of the gastric fundus under hypochlorhydric conditions. J Pathol. 2007;213:161–169
  14. El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404:398–402
  15. Tu S, Bhagat G, Cui G, et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 2008;14:408–419
  16. El-Omar EM. The importance of interleukin 1beta in Helicobacter pylori associated disease. Gut. 2001;48:743–747
  17. Dimmler A, Brabletz T, Hlubek F, et al. Transcription of sonic hedgehog, a potential factor for gastric morphogenesis and gastric mucosa maintenance, is up-regulated in acidic conditions. Lab Invest. 2003;83:1829–1837
  18. El-Zaatari M, Grabowska AM, McKenzie AJ, et al. Cyclopamine inhibition of the sonic hedgehog pathway in the stomach requires concomitant acid inhibition. Regul Pept. 2008;146:131–139
  19. Zavros Y, Waghray M, Tessier A, et al. Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation. J Biol Chem. 2007;282:33265–33274
  20. Jeong J, Mao J, Tenzen T, et al. Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia. Genes Dev. 2004;18:937–951
  21. Muraoka A, Kaise M, Guo YJ, et al. Canine H(+)-K(+)-ATPase alpha-subunit gene promoter: studies with canine parietal cells in primary culture. Am J Physiol. 1996;271:G1104–G1113
  22. Soll AH. The actions of secretagogues on oxygen uptake by isolated mammalian parietal cells. J Clin Invest. 1978;61:370–380
  23. Boland CR, Kraus ER, Scheiman JM, et al. Characterization of mucous cell synthetic functions in a new primary canine gastric mucous cell culture system. Am J Physiol. 1990;258:G774–G787
  24. Chew CS, Ljungstrom M, Smolka A, et al. Primary culture of secretagogue-responsive parietal cells from rabbit gastric mucosa. Am J Physiol. 1989;256:G254–G263
  25. Franic TV, Judd LM, Robinson D, et al. Regulation of gastric epithelial cell development revealed in H(+)/K(+)-ATPase beta-subunit- and gastrin-deficient mice. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1502–G1511
  26. Judd LM, Andringa A, Rubio CA, et al. Gastric achlorhydria in H/K-ATPase-deficient (Atp4a(-/-)) mice causes severe hyperplasia, mucocystic metaplasia and upregulation of growth factors. J Gastroenterol Hepatol. 2005;20:1266–1278
  27. Remy C, Kirchhoff P, Hafner P, et al. Stimulatory pathways of the calcium-sensing receptor on acid secretion in freshly isolated human gastric glands. Cell Physiol Biochem. 2007;19:33–42
  28. Schepp W, Dehne K, Herrmuth H, et al. Identification and functional importance of IL-1 receptors on rat parietal cells. Am J Physiol. 1998;275:G1094–G1105
  29. Karam SM, Yao X, Forte JG. Functional heterogeneity of parietal cells along the pit-gland axis. Am J Physiol. 1997;272:G161–G171
  30. Beales IL, Calam J. Interleukin 1 beta and tumour necrosis factor alpha inhibit acid secretion in cultured rabbit parietal cells by multiple pathways. Gut. 1998;42:227–234
  31. El-Omar EM, Carrington M, Chow WH, et al. The role of interleukin-1 polymorphisms in the pathogenesis of gastric cancer. Nature. 2001;412:99
  32. Wallace JL, Cucala M, Mugridge K, et al. Secretagogue-specific effects of interleukin-1 on gastric acid secretion. Am J Physiol. 1991;261:G559–G564
  33. Stepan V, Ramamoorthy S, Nitsche H, et al. Regulation and function of the sonic hedgehog signal transduction pathway in isolated gastric parietal cells. J Biol Chem. 2005;280:15700–15708
  34. Lu HC, Swindell EC, Sierralta WD, et al. Evidence for a role of protein kinase C in FGF signal transduction in the developing chick limb bud. Development. 2001;128:2451–2460

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by NIH grants P01 DK62041 (J.L.M.) and R56 DK058312-06A2 (A.T.).

PII: S0016-5085(09)01940-4

doi: 10.1053/j.gastro.2009.10.043

Gastroenterology
Volume 138, Issue 2 , Pages 562-572.e2 , February 2010

Article Tools

* Image Usage & Resolution