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Abdel-Aziz H, Schneider M, Neuhuber W, et al. GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis. Mol Med. 2016;21(1):1011-1024doi: 10.2119/molmed.2015.00098.
Abdel-Aziz, H., Schneider, M., Neuhuber, W., Meguid Kassem, A., Khailah, S., Müller, J., Gamal Eldeen, H., Khairy, A., T Khayyal, M., Shcherbakova, A., Efferth, T., & Ulrich-Merzenich, G. (2016). GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis. Molecular medicine (Cambridge, Mass.), 21(1), 1011-1024. https://doi.org/10.2119/molmed.2015.00098
Abdel-Aziz, Heba, et al. "GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis." Molecular medicine (Cambridge, Mass.) vol. 21,1 (2016): 1011-1024. doi: https://doi.org/10.2119/molmed.2015.00098
Abdel-Aziz H, Schneider M, Neuhuber W, Meguid Kassem A, Khailah S, Müller J, Gamal Eldeen H, Khairy A, T Khayyal M, Shcherbakova A, Efferth T, Ulrich-Merzenich G. GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis. Mol Med. 2016 Aug;21(1):1011-1024. doi: 10.2119/molmed.2015.00098. Epub 2016 May 09. PMID: 26650186; PMCID: PMC4982478.
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Mol Med. 2016 Aug;21(1):1011-1024. doi: 10.2119/molmed.2015.00098. Epub 2016 May 09.

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

Molecular medicine (Cambridge, Mass.)

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

Affiliations

  1. Department of Pharmacology, Institute of Pharmaceutical Chemistry, Westfalian Wilhelms University, Münster, Germany.
  2. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
  3. Institute of Anatomy, University of Erlangen-Nürnberg, Erlangen, Germany.
  4. Tropical Medicine Department and Gastrointestinal Endoscopy Unit, Faculty of Medicine, Cairo University, Cairo, Egypt.
  5. Scientific Department, Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany.
  6. Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  7. Medical Clinic III, University Clinic Centre, Rheinische Friedrich-Wilhelms University, Bonn, Germany.

PMID: 26650186 PMCID: PMC4982478 DOI: 10.2119/molmed.2015.00098

Abstract

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.

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