Prostacyclin signaling regulates circulating ghrelin during acute inflammation

Lisa D. Madison, Jarrad M. Scarlett, Peter Levasseur, Xin Xia Zhu, Kenneth Newcomb, Ayesha Batra, Darren Bowe, Daniel L. Marks

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Ghrelin is an octanoylated 28 amino acid peptide predominantly secreted by the stomach, and has potent stimulatory effects on appetite. Several laboratories, including our own, have demonstrated that ghrehn levels fall in states of acute inflammation brought about by injection of bacterial lipopolysaccharide (LPS). We now demonstrate that the decrease in circulating ghrelin is not due to a decrease in ghrelin gene expression, but is instead likely to be due to an acute decrease in ghrelin secretion. Furthermore, we have found that the change in circulating ghrelin during acute inflammation required a prostaglandin second messenger, but did not require the synthesis of nitric oxide. Interestingly, i.v. injection of prostaglandin E2 failed to decrease circulating ghrelin levels, whereas prostacyclin decreased circulating ghrelin to a similar extent as did LPS. We also provide anatomical evidence for the mechanism of the regulation of ghrelin by inflammation. We demonstrate that the type 1 interleukin-1β (IL-1β) receptor is expressed within the gastric mucosa, but is not expressed by ghrelin cells. The prostacyclin receptor was also expressed in the gastric mucosa, and the majority of ghrelin-producing cells were found to co-express this receptor. Mice with genetic deletion of the type 1 IL-1 receptor do not suppress circulating ghrelin levels with LPS administration. Collectively, these data support a model in which the mechanism of inflammation induced decreases in ghrelin are due to the action of IL-1β on cells within the gastric mucosa that in turn produce prostacyclin as a second messenger. These data provide further support for the potential role of ghrelin as a therapeutic agent in acute and chronic inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)263-273
Number of pages11
JournalJournal of Endocrinology
Issue number2
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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