Details

Autor(en) / Beteiligte

• Abdel-Aziz, Heba
• Schneider, Mathias
• Neuhuber, Winfried
• Meguid Kassem, Abdel
• Khailah, Saleem
• Müller, Jürgen
• Gamal Eldeen, Hadeel
• Khairy, Ahmed
• T Khayyal, Mohamed
• Shcherbakova, Anastasiia
• Efferth, Thomas
• Ulrich-Merzenich, Gudrun

Titel

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

Ist Teil von

• Molecular medicine (Cambridge, Mass.), 2015-01, Vol.21 (1), p.1011-1024

Ort / Verlag

England: BioMed Central

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.org.