Interferon-γ Inhibits Ghrelin Expression and Secretion Via a Somatostatin-mediated Mechanism

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2011 Sep 14

PMID 21912454

Citations 4

Authors

Jesper A B Strickertsson

Kristina B V Dossing

Anna J M Aabakke

Hans-Olof Nilsson

Thomas V O Hansen

Ulrich Knigge

Andreas Kjaer

Torkel Wadstrom

Lennart Friis-Hansen

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate if and how the proinflammatory cytokine interferon γ (IFNγ) affects ghrelin expression in mice.

Methods: The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were examined in wild-type mice and mice infected with Helicobacter pylori (H. pylori). Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ alone, mice were given a subcutaneous infusion of IFNγ for 7 d. Finally, the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.

Results: H. pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models. Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.

Conclusion: Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression. IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.

Citing Articles

UPLC-Q-TOF/MS-Based Serum and Urine Metabonomics Study on the Ameliorative Effects of Palmatine on -Induced Chronic Atrophic Gastritis.

Chen X, Zhang J, Wang R, Liu H, Bao C, Wu S Front Pharmacol. 2020; 11:586954.

PMID: 33041831 PMC: 7522567. DOI: 10.3389/fphar.2020.586954.

Network-driven plasma proteomics expose molecular changes in the Alzheimer's brain.

Jaeger P, Lucin K, Britschgi M, Vardarajan B, Huang R, Kirby E Mol Neurodegener. 2016; 11:31.

PMID: 27112350 PMC: 4845325. DOI: 10.1186/s13024-016-0095-2.

Serum ghrelin; a new surrogate marker of gastric mucosal alterations in upper gastrointestinal carcinogenesis.

Sadjadi A, Yazdanbod A, Lee Y, Boreiri M, Samadi F, Alizadeh B PLoS One. 2013; 8(9):e74440.

PMID: 24098650 PMC: 3787044. DOI: 10.1371/journal.pone.0074440.

The effects of fever on hormone ghrelins, immunoglobulins, and heat shock protein 70 expression after swine flu vaccinations.

Aydin S, Guven T, Sahin I, Aksoy A, Kendir Y, Ilhan M Endocrine. 2012; 42(2):352-8.

PMID: 22477150 PMC: 7090797. DOI: 10.1007/s12020-012-9664-5.

References

Tomasetto C, Karam S, Ribieras S, Masson R, Lefebvre O, Staub A . Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide. Gastroenterology. 2000; 119(2):395-405. DOI: 10.1053/gast.2000.9371. View

Kirchner H, Tong J, Tschop M, Pfluger P . Ghrelin and PYY in the regulation of energy balance and metabolism: lessons from mouse mutants. Am J Physiol Endocrinol Metab. 2010; 298(5):E909-19. DOI: 10.1152/ajpendo.00191.2009. View

Isomoto H, Nakazato M, Ueno H, Date Y, Nishi Y, Mukae H . Low plasma ghrelin levels in patients with Helicobacter pylori-associated gastritis. Am J Med. 2004; 117(6):429-32. DOI: 10.1016/j.amjmed.2004.01.030. View

Zavros Y, Paterson A, Lambert J, Shulkes A . Expression of progastrin-derived peptides and somatostatin in fundus and antrum of nonulcer dyspepsia subjects with and without Helicobacter pylori infection. Dig Dis Sci. 2000; 45(10):2058-64. DOI: 10.1023/a:1005659104779. View

Gotz J, Veenendaal R, Biemond I, Muller E, Veselic M, Lamers C . Serum gastrin and mucosal somatostatin in Helicobacter pylori-associated gastritis. Scand J Gastroenterol. 1995; 30(11):1064-8. DOI: 10.3109/00365529509101608. View

Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal M, Suganuma T . Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000; 141(11):4255-61. DOI: 10.1210/endo.141.11.7757. View

Wiedemann T, Loell E, Mueller S, Stoeckelhuber M, Stolte M, Haas R . Helicobacter pylori cag-Pathogenicity island-dependent early immunological response triggers later precancerous gastric changes in Mongolian gerbils. PLoS One. 2009; 4(3):e4754. PMC: 2650263. DOI: 10.1371/journal.pone.0004754. View

Isomoto H, Ueno H, Saenko V, Mondal M, Nishi Y, Kawano N . Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am J Gastroenterol. 2005; 100(8):1711-20. DOI: 10.1111/j.1572-0241.2005.41492.x. View

Sundler F, Andersson K, Mattsson H . Administration of omeprazole to rats for one year produces reciprocal effects on antral gastrin and somatostatin cells and no effect on endocrine cells in the colon. Digestion. 1995; 56(3):194-8. DOI: 10.1159/000201242. View

10.

Tschop M, Wawarta R, Riepl R, Friedrich S, Bidlingmaier M, Landgraf R . Post-prandial decrease of circulating human ghrelin levels. J Endocrinol Invest. 2001; 24(6):RC19-21. DOI: 10.1007/BF03351037. View

11.

Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T . Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001; 86(10):4753-8. DOI: 10.1210/jcem.86.10.7885. View

12.

Isomoto H, Ueno H, Nishi Y, Yasutake T, Tanaka K, Kawano N . Circulating ghrelin levels in patients with various upper gastrointestinal diseases. Dig Dis Sci. 2005; 50(5):833-8. DOI: 10.1007/s10620-005-2648-z. View

13.

Suzuki H, Hibi T . Does Helicobacter pylori attack ghrelin-producing cells?. J Gastroenterol. 2005; 40(4):437-9. DOI: 10.1007/s00535-005-1568-1. View

14.

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

15.

Friis-Hansen L, Rieneck K, Nilsson H, Wadstrom T, Rehfeld J . Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice. Gastroenterology. 2006; 131(1):246-58. DOI: 10.1053/j.gastro.2006.04.031. View

16.

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K . Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402(6762):656-60. DOI: 10.1038/45230. View

17.

Ukkola O . Ghrelin and the metabolic balance. J Endocrinol Invest. 2005; 28(9):849-52. DOI: 10.1007/BF03347580. View

18.

Smythies L, Waites K, Lindsey J, Harris P, Ghiara P, Smith P . Helicobacter pylori-induced mucosal inflammation is Th1 mediated and exacerbated in IL-4, but not IFN-gamma, gene-deficient mice. J Immunol. 2000; 165(2):1022-9. DOI: 10.4049/jimmunol.165.2.1022. View

19.

Konturek P, Brzozowski T, Konturek S, Stachura J, Karczewska E, Pajdo R . Mouse model of Helicobacter pylori infection: studies of gastric function and ulcer healing. Aliment Pharmacol Ther. 1999; 13(3):333-46. DOI: 10.1046/j.1365-2036.1999.00476.x. View

20.

Bravo L, Mera R, Reina J, Pradilla A, Alzate A, Fontham E . Impact of Helicobacter pylori infection on growth of children: a prospective cohort study. J Pediatr Gastroenterol Nutr. 2003; 37(5):614-9. DOI: 10.1097/00005176-200311000-00021. View