Green, N.H. orcid.org/0000-0001-5413-0642, Huang, Q.Z., Corfe, B.M. et al. (2 more authors) (2011) NF-kappa B is activated in oesophageal fibroblasts in response to a paracrine signal generated by acid-exposed primary oesophageal squamous cells. International Journal of Experimental Pathology, 92 (5). pp. 345-356. ISSN 0959-9673
Abstract
Oesophageal exposure to duodenogastro-oesophageal refluxate leads to reflux oesophagitis and is implicated in the development of Barrett’s metaplasia (BM). NF-κB signalling in epithelial cells is associated with the activation of transcription factors believed to be central to BM development, whilst NF-κB activation in fibroblasts plays a critical role in matrix remodelling. Our aim was to study the effects of acid exposure on NF-κB activation in primary human oesophageal fibroblasts (HOFs) and primary and immortalized oesophageal squames and to investigate any epithelial/stromal interactions in the response of these cells to acid. Primary HOFs and primary and immortalized oesophageal epithelial cells were exposed to acid (pH 7 – pH 4 ≤ 120 min) in single or pulsed treatments. Conditioned medium from epithelial cells following acid exposure was also applied to fibroblasts. Cell viability was determined by MTT-ESTA. NF-κB activation was determined by cellular localization of NF-κB/p65 visualized by immunofluorescence. Conditioned medium from oesophageal epithelial cells, subjected to pH 5 pulsatile exposure, activated NF-κB in fibroblasts, with some inter-patient variability, but these conditions did not directly activate NF-κB in the epithelial cells themselves. Significant NF-κB activation was seen in the epithelial cells but only with greater acidity and exposure times (pH 4, 60–120 min). Our findings show that acid exposure can cause indirect activation of stromal cells by epithelial–stromal interactions. This may contribute to the pathogenesis of oesophageal diseases, and the inter-patient variability may go some way to explain why some patients with reflux oesophagitis develop BM and others do not.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2011 International Journal of Experimental Pathology. This is an author produced version of a paper subsequently published in International Journal of Experimental Pathology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | acid; Barrett's Metaplasia; NF-kappa B; oesophageal adenocarcinoma; paracrine; reflux; BARRETTS-ESOPHAGUS; GENE-EXPRESSION; IN-VITRO; NEOADJUVANT CHEMORADIOTHERAPY; HUMAN KERATINOCYTES; EPITHELIAL-CELLS; CDX2; ADENOCARCINOMA; DIFFERENTIATION; METAPLASIA |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Materials Science and Engineering (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Apr 2016 14:16 |
Last Modified: | 20 Apr 2016 04:10 |
Published Version: | http://dx.doi.org/10.1111/j.1365-2613.2011.00778.x |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/j.1365-2613.2011.00778.x |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97004 |