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.
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: Javier Molina-Infante; Lucia Ferrando-Lamana; Cristina Ripoll; Moises Hernandez-Alonso; Jose M Mateos; Miguel Fernandez-Bermejo; Carmen Dueñas; Nuria Fernandez-Gonzalez; Eva M Quintana; Maria Angeles Gonzalez-Nuñez Journal: Clin Gastroenterol Hepatol Date: 2010-10-01 Impact factor: 11.382
Authors: Chris A Liacouras; Glenn T Furuta; Ikuo Hirano; Dan Atkins; Stephen E Attwood; Peter A Bonis; A Wesley Burks; Mirna Chehade; Margaret H Collins; Evan S Dellon; Ranjan Dohil; Gary W Falk; Nirmala Gonsalves; Sandeep K Gupta; David A Katzka; Alfredo J Lucendo; Jonathan E Markowitz; Richard J Noel; Robert D Odze; Philip E Putnam; Joel E Richter; Yvonne Romero; Eduardo Ruchelli; Hugh A Sampson; Alain Schoepfer; Nicholas J Shaheen; Scott H Sicherer; Stuart Spechler; Jonathan M Spergel; Alex Straumann; Barry K Wershil; Marc E Rothenberg; Seema S Aceves Journal: J Allergy Clin Immunol Date: 2011-04-07 Impact factor: 10.793
Authors: Kathryn A Peterson; Kristen L Thomas; Kristen Hilden; Lyska L Emerson; Jason C Wills; John C Fang Journal: Dig Dis Sci Date: 2009-06-18 Impact factor: 3.199
Authors: Jonathan M Spergel; Evan S Dellon; Chris A Liacouras; Ikuo Hirano; Javier Molina-Infante; Albert J Bredenoord; Glenn T Furuta Journal: Ann Allergy Asthma Immunol Date: 2018-07-18 Impact factor: 6.347
Authors: Xiaofang Huo; Xi Zhang; Chunhua Yu; Qiuyang Zhang; Edaire Cheng; David H Wang; Thai H Pham; Stuart J Spechler; Rhonda F Souza Journal: Gut Date: 2013-09-18 Impact factor: 23.059
Authors: Mirna Chehade; Stacie M Jones; Robbie D Pesek; A Wesley Burks; Brian P Vickery; Robert A Wood; Donald Y M Leung; Glenn T Furuta; David M Fleischer; Alice K Henning; Peter Dawson; Robert W Lindblad; Scott H Sicherer; J Pablo Abonia; Joseph D Sherrill; Hugh A Sampson; Marc E Rothenberg Journal: J Allergy Clin Immunol Pract Date: 2018-08-01