Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism

Figure 1 Mice infected with Helicobacter pylori have reduced ghrelin expression and do not gain weight. C57BL6/J mice were infected with Helicobacter pylori (H. pylori) strain 67:21 [this strain is VacA+ and contains a complete genetically stable Cag pathogenicity island (PAI)]. While the control mice gained weight the infected mice did not (A). Mice infected with H. pylori had reduced ghrelin expression in the stomach (B) and reduced ghrelin plasma concentrations (C). ^aP < 0.05 vs control.

Figure 2 Interferon γ expression is increased and ghrelin expression is reduced in old but not young gastrin knockout mice and histidine decarboxylase knockout mice. The expression of interferon γ (IFNγ) and ghrelin mRNA in young (12-16 wk) and old (48-56 wk) achlorhydric gastrin KO mice and old (48-56 wk) hypochlorhydric histidine decarboxylase (HDC) KO mice (n = 6 in each group) is shown. There is no change in either IFNγ (A) or ghrelin (B) expression in HDC KO mice as compared to wt mice. While the gastric inflammation evaluated by expression of IFNγ increases when the gastrin KO mice get older (C), the expression of ghrelin decreases (D). ^aP < 0.05.

Figure 3 Interferon γ suppresses ghrelin expression in the gastric fundus and ghrelin concentrations in plasma independently of loss of ghrelin-producing cells. Mice infused with interferon γ (IFNγ) as compared to saline infused mice (n = 6 in each group). IFNγ was infused at low dose (LD) = 8 μg/kg per hour for 7 d or high dose (HD) = 24 μg/kg per hour for 7 d. Low (A) and high (B) dose IFNγ infusion decreases the expression of ghrelin mRNA to a similar degree. HD IFNγ represses ghrelin concentrations in plasma gradually over time (C). The density of fundic ghrelin cells is not altered by IFNγ infusion (D). ^aP < 0.05.

Figure 4 The somatostatin receptor agonist octreotide inhibits activation of the ghrelin promoter. Pulmonary carcinoid NCI-H727 cells were transfected with a 2 kb mouse ghrelin promoter construct and treated for 24 h with forskolin, IBMX, octreotide, and interferon γ (IFNγ) alone or in combination, after which the ghrelin promoter response was measured by the dual-luciferase reporter assay system. Octreotide inhibited both basal and IBMX and/or forskolin-induced ghrelin expression. Forskolin and IBMX were dissolved in dimethyl sulfoxide (DMSO). ^aP < 0.05.