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Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD.
Gut 2013; 62(6):824-32Gut

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.

DESIGN

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.

CONCLUSION

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+Show Affiliations

Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Medical Center, Dallas, Texas, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22580413

Citation

Cheng, Edaire, et al. "Omeprazole Blocks Eotaxin-3 Expression By Oesophageal Squamous Cells From Patients With Eosinophilic Oesophagitis and GORD." Gut, vol. 62, no. 6, 2013, pp. 824-32.
Cheng E, Zhang X, Huo X, et al. Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut. 2013;62(6):824-32.
Cheng, E., Zhang, X., Huo, X., Yu, C., Zhang, Q., Wang, D. H., ... Souza, R. F. (2013). Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut, 62(6), pp. 824-32. doi:10.1136/gutjnl-2012-302250.
Cheng E, et al. Omeprazole Blocks Eotaxin-3 Expression By Oesophageal Squamous Cells From Patients With Eosinophilic Oesophagitis and GORD. Gut. 2013;62(6):824-32. PubMed PMID: 22580413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. AU - Cheng,Edaire, AU - Zhang,Xi, AU - Huo,Xiaofang, AU - Yu,Chunhua, AU - Zhang,Qiuyang, AU - Wang,David H, AU - Spechler,Stuart Jon, AU - Souza,Rhonda F, Y1 - 2012/05/12/ PY - 2012/5/15/entrez PY - 2012/5/15/pubmed PY - 2013/7/3/medline SP - 824 EP - 32 JF - Gut JO - Gut VL - 62 IS - 6 N2 - 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. DESIGN: 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. CONCLUSION: 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. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/22580413/Omeprazole_blocks_eotaxin_3_expression_by_oesophageal_squamous_cells_from_patients_with_eosinophilic_oesophagitis_and_GORD_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=22580413 DB - PRIME DP - Unbound Medicine ER -