University of Oulu

Nortunen, M., Väkiparta, N., Porvari, K. et al. Pathophysiology of reflux oesophagitis: role of Toll-like receptors 2 and 4 and Farnesoid X receptor. Virchows Arch 479, 285–293 (2021).

Pathophysiology of reflux oesophagitis : role of Toll-like receptors 2 and 4 and Farnesoid X receptor

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Author: Nortunen, Minna1,2,3; Väkiparta, Nina1; Porvari, Katja1;
Organizations: 1Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, 90014, Oulu, Finland
2Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland
3Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-10-27


The pathogenesis of gastroesophageal reflux disease (GERD) is not fully understood. It involves the activation of mucosal immune-mediated and inflammatory responses. Toll-like receptors (TLR) 2 and TLR4 are pattern-recognition receptors of the innate immune system; they recognize microbial and endogenous ligands. Farnesoid X receptor (FXR) is a bile acid receptor that regulates the inflammatory response. We aimed to evaluate TLR2, TLR4 and FXR expression patterns in GERD. We re-evaluated 84 oesophageal biopsy samples according to the global severity (GS) score, including 26 cases with histologically normal oesophagus, 28 with histologically mild oesophagitis and 30 with severe oesophagitis. We used immunohistochemistry and in situ hybridization to assess the expression patterns of TLR2, TLR4 and FXR in oesophageal squamous cells. Immunohistochemistry showed that nuclear and cytoplasmic TLR2 was expressed predominantly in the basal layer of normal oesophageal epithelium. In oesophagitis, TLR2 expression increased throughout the epithelium, and the superficial expression was significantly more intensive compared to normal epithelium, p <0.01. Nuclear and cytoplasmic TLR4 was expressed throughout the thickness of squamous epithelium, with no change in oesophagitis. FXR was expressed in the nuclei of squamous cells, and the intensity of the expression increased significantly in oesophagitis (p <0.05). FXR expression correlated with basal TLR2. In situ hybridization confirmed the immunohistochemical expression patterns of TLR2 and TLR4. In GERD, TLR2, but not TLR4, expression was upregulated which indicates that innate immunity is activated according to a specific pattern in GERD. FXR expression was increased in GERD and might have a regulatory connection to TLR2.

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Series: Virchows Archiv. European journal of pathology
ISSN: 0945-6317
ISSN-E: 1432-2307
ISSN-L: 0945-6317
Volume: 479
Issue: 2
Pages: 285 - 293
DOI: 10.1007/s00428-021-03066-w
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: Open access funding provided by University of Oulu including Oulu University Hospital. This study was funded by Finnish Government Research Funding (MN), Academy of Finland (HH), Vieno and Alli Suorsa Health Care Foundation (HH) and Thelma Mäkikyrö Foundation (HH).
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