title: Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD.
abstract: OBJECTIVE
  Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) can have similar clinical and histological features. Proton pump inhibitors (PPIs) are used to distinguish the disorders, with the assumption that only GORD can respond to PPIs. Oesophageal expression of eotaxin-3 stimulated by Th2 cytokines might contribute to oesophageal eosinophilia in EoE. Th2 cytokine effects on the oesophagus in GORD are not known. The objective of the authors was to explore the molecular mechanisms of Th2 cytokines on eotaxin-3 expression by oesophageal squamous cells from patients with GORD and EoE, and the effects of omeprazole on that eotaxin-3 expression.
  
  
  METHODS
  Using telomerase-immortalised and primary cultures of oesophageal squamous cells from GORD and EoE patients, the authors measured eotaxin-3 protein secretion stimulated by Th2 cytokines (interleukin (IL)-4 and IL-13). Eotaxin-3 promoter constructs were used to study transcriptional regulation. Cytokine-induced eotaxin-3 mRNA and protein expression were measured in the presence or absence of omeprazole.
  
  
  RESULTS
  There were no significant differences between EoE and GORD primary cells in cytokine-stimulated eotaxin-3 protein secretion levels. In EoE and GORD cell lines, IL-4 and IL-13 activated the eotaxin-3 promoter, and significantly increased eotaxin-3 mRNA and protein expression. Omeprazole blocked the cytokine-stimulated increase in eotaxin-3 mRNA and protein expression in EoE and GORD cell lines.
  
  
  CONCLUSIONS
  Oesophageal squamous cells from GORD and EoE patients express similar levels of eotaxin-3 when stimulated by Th2 cytokines, and omeprazole blocks that eotaxin-3 expression. These findings suggest that PPIs might have eosinophil-reducing effects independent of effects on acid reflux and that response to PPIs might not distinguish EoE from GORD.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Medical Center, Dallas, Texas, USA.
authors.forename: Edaire
authors.initials: E
authors.lastname: Cheng
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Huo
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yu
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Zhang
authors.forename: David H
authors.initials: DH
authors.lastname: Wang
authors.forename: Stuart Jon
authors.initials: SJ
authors.lastname: Spechler
authors.forename: Rhonda F
authors.initials: RF
authors.lastname: Souza
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D057765:Eosinophilic Esophagitis / Q000188:drug therapy* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004947:Esophagus / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018418:Th2 Cells / Q000502:physiology
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D015847:Interleukin-4; D009853:Omeprazole