4.3 Article

Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis

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出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPG.0000000000002144

关键词

eosinophil; eosinophilic esophagitis; epithelial barrier; IL-9; remodeling

资金

  1. NIH/NIAID [AI 135034, AI 092135]
  2. Rady Children's Hospital Academic Enrichment Grant
  3. NIH [UL1TR001442]
  4. NIH/NCRR/NCATS [UL1TR000039]

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Background: Eosinophilic esophagitis (EoE) is a chronic Th2-assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of interleukin 9 (IL-9) expressing inflammatory cells. While IL-9 is known to affect barrier function in the intestine, the functional effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE. Methods: We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL-9 receptor, the adherens junction protein E-cadherin and the tight junction protein claudin-1. We treated primary human esophageal epithelial cells with IL-9 to understand its effects on E-cadherin expression and function. Results: Active EoE subjects had increased epithelial expression of IL-9 receptor mRNA and protein (P < 0.05) and decreased membrane bound E-cadherin (P < 0.01) and claudin-1 (P < 0.05) expression. IL-9 receptor expression and mislocalized claudin-1 positively correlated and while membrane bound E-cadherin expression negatively correlated with the degree of histologic epithelial remodeling (P < 0.05). IL-9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (P < 0.01) and membrane bound E-cadherin in epithelial cell monolayers (P < 0.01). Conclusions: These data suggest that IL-9, its receptor, and its effects on E-cadherin may be important mechanisms for epithelial barrier disruption in EoE.

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