Endogenous glucocorticoids prevent gastric metaplasia by suppressing spontaneous inflammation.

Published

Journal Article

In the stomach, chronic inflammation causes metaplasia and creates a favorable environment for the evolution of gastric cancer. Glucocorticoids are steroid hormones that repress proinflammatory stimuli, but their role in the stomach is unknown. In this study, we show that endogenous glucocorticoids are required to maintain gastric homeostasis. Removal of circulating glucocorticoids in mice by adrenalectomy resulted in the rapid onset of spontaneous gastric inflammation, oxyntic atrophy, and spasmolytic polypeptide-expressing metaplasia (SPEM), a putative precursor of gastric cancer. SPEM and oxyntic atrophy occurred independently of lymphocytes. However, depletion of monocytes and macrophages by clodronate treatment or inhibition of gastric monocyte infiltration using the Cx3cr1 knockout mouse model prevented SPEM development. Our results highlight the requirement for endogenous glucocorticoid signaling within the stomach to prevent spontaneous gastric inflammation and metaplasia, and suggest that glucocorticoid deficiency may lead to gastric cancer development.

Full Text

Duke Authors

Cited Authors

  • Busada, JT; Ramamoorthy, S; Cain, DW; Xu, X; Cook, DN; Cidlowski, JA

Published Date

  • March 1, 2019

Published In

Volume / Issue

  • 129 / 3

Start / End Page

  • 1345 - 1358

PubMed ID

  • 30652972

Pubmed Central ID

  • 30652972

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI123233

Language

  • eng

Conference Location

  • United States