Copyright
©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism
Jesper AB Strickertsson, Kristina BV Døssing, Anna JM Aabakke, Hans-Olof Nilsson, Thomas VO Hansen, Ulrich Knigge, Andreas Kjær, Torkel Wadström, Lennart Friis-Hansen
Jesper AB Strickertsson, Kristina BV Døssing, Anna JM Aabakke, Thomas VO Hansen, Lennart Friis-Hansen, Genomic Medicine, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
Jesper AB Strickertsson, Department of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
Hans-Olof Nilsson, Torkel Wadström, Department of Microbiology, University of Lund, Lund, Sweden.
Ulrich Knigge, Department of Gastro-Intestinal Surgery, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
Andreas Kjær, Department of Clinical Physiology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
Author contributions: Strickertsson JAB designed the study, performed the promoter studies, and wrote the paper; Døssing KBV provided the cell lines; Aabakke AJM performed the immunohistochemical analysis; Nilsson HO designed the infection studies, handled the bacterial cultures, performed the infection studies, and interpreted the data; Hansen TVO designed and supervised the promoter study; Knigge U provided the wt and HDC KO mice; Kjær A provided the wt and HDC KO mice; Wadström T designed the study, provided the bacterial cultures, supervised the experiments, interpreted the data, and wrote the paper; Friis-Hansen L designed the study, provided the wt and gastrin KO mice, supervised the experiments, interpreted the data, and wrote the paper.
Supported by The Danish MRC Grant 271-08-0378 (LFH), the ALF grant (TW), The Lundbeck foundation (KBVD)
Correspondence to: Lennart Friis-Hansen, MD, DMSc, Genomic Medicine, Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, KB-3014, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. lfh@rh.dk
Telephone: +45-35-455509 Fax: +45-35-454640
Received: December 21, 2010
Revised: March 5, 2011
Accepted: March 12, 2011
Published online: July 14, 2011
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.
