Gastroesophageal Reflux Might Cause Esophagitis Through a Cytokine-Mediated Mechanism Rather Than Caustic Acid Injury

Rhonda F. Souza, Xiaofang Huo, Vivek Mittal, Christopher M. Schuler, Susanne W. Carmack, Hui Ying Zhang, Xi Zhang, Chunhua Yu, Kathy Hormi-Carver, Robert M. Genta, Stuart J. Spechler

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

Background & Aims: Reflux esophagitis is believed to be caused by the caustic effects of refluxed gastric acid on esophageal epithelial cells. However, caustic chemical injuries develop rapidly whereas esophagitis might not appear until weeks after the induction of reflux in animal models. We studied early histologic events in the development of reflux esophagitis in a rat model and performed in vitro experiments to determine whether exposure to acidified bile salts causes esophageal epithelial cells to secrete chemokines that might contribute to inflammation. Methods: At various time points after esophagoduodenostomy, the rat esophagus was removed and inflammatory changes were analyzed by histologic analyses. Human esophageal squamous cell lines were exposed to acidified bile salts to evaluate their effects on cytokine production and immune-cell migration. Results: Reflux esophagitis started at postoperative day 3 with lymphocytic infiltration of the submucosa that progressed to the epithelial surface-these findings contradicted those expected from a caustic chemical injury. Basal cell and papillary hyperplasia preceded the development of surface erosions. Exposure of squamous cells to acidified bile salts significantly increased the secretion of interleukin-8 and interleukin-1β; conditioned media from these cells caused significant increases in the migration rates of T cells and neutrophils. Conclusions: These findings support, but do not prove, an alternative concept for the development of reflux esophagitis in which refluxed gastric juice does not directly damage the esophagus, but rather stimulates esophageal epithelial cells to secrete chemokines that mediate damage of esophageal tissue.

Original languageEnglish (US)
Pages (from-to)1776-1784
Number of pages9
JournalGastroenterology
Volume137
Issue number5
DOIs
StatePublished - Nov 2009

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Caustics
Esophagitis
Gastroesophageal Reflux
Peptic Esophagitis
Epithelial Cells
Cytokines
Bile Acids and Salts
Acids
Wounds and Injuries
Chemokines
Esophagus
Gastric Juice
Gastric Acid
Conditioned Culture Medium
Interleukin-8
Interleukin-1
Cell Movement
Hyperplasia
Neutrophils
Animal Models

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Gastroesophageal Reflux Might Cause Esophagitis Through a Cytokine-Mediated Mechanism Rather Than Caustic Acid Injury. / Souza, Rhonda F.; Huo, Xiaofang; Mittal, Vivek; Schuler, Christopher M.; Carmack, Susanne W.; Zhang, Hui Ying; Zhang, Xi; Yu, Chunhua; Hormi-Carver, Kathy; Genta, Robert M.; Spechler, Stuart J.

In: Gastroenterology, Vol. 137, No. 5, 11.2009, p. 1776-1784.

Research output: Contribution to journalArticle

Souza, Rhonda F. ; Huo, Xiaofang ; Mittal, Vivek ; Schuler, Christopher M. ; Carmack, Susanne W. ; Zhang, Hui Ying ; Zhang, Xi ; Yu, Chunhua ; Hormi-Carver, Kathy ; Genta, Robert M. ; Spechler, Stuart J. / Gastroesophageal Reflux Might Cause Esophagitis Through a Cytokine-Mediated Mechanism Rather Than Caustic Acid Injury. In: Gastroenterology. 2009 ; Vol. 137, No. 5. pp. 1776-1784.
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