GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Heba Abdel-Aziz
- Mathias Schneider
- Winfried Neuhuber
- Abdel Meguid Kassem
- Saleem Khailah
- Juergen Mueller
- Hadeel Gamal Eldeen
- Ahmed Khairy
- Mohamed T Khayyal
- Anastasiia Shcherbakova
- Thomas Efferth
- Gudrun Ulrich-Merzenich
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000377271200032&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.2119/molmed.2015.00098
- eISSN
- 1528-3658
- Externe Identifier
- Clarivate Analytics Document Solution ID: DN7QE
- PubMed Identifier: 26650186
- ISSN
- 1076-1551
- Zeitschrift
- MOLECULAR MEDICINE
- Paginierung
- 1011 - 1024
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis
- Sub types
- Article
- Ausgabe der Zeitschrift
- 21
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- 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
- DOI
- 10.2119/molmed.2015.00098
- eISSN
- 1528-3658
- ISSN
- 1076-1551
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Molecular Medicine
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 1011 - 1024
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.2119/molmed.2015.00098
- Datum der Datenerfassung
- 2019
- Titel
- GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis
- Ausgabe der Zeitschrift
- 21
Datenquelle: Crossref
- 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.
- Addresses
- Department of Pharmacology, Institute of Pharmaceutical Chemistry, Westfalian Wilhelms University, Münster, Germany.
- Autoren
- 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
- Thomas Efferth
- Gudrun Ulrich-Merzenich
- DOI
- 10.2119/molmed.2015.00098
- eISSN
- 1528-3658
- Externe Identifier
- PubMed Identifier: 26650186
- PubMed Central ID: PMC4982478
- Open access
- false
- ISSN
- 1076-1551
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Molecular medicine (Cambridge, Mass.)
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2016
- Paginierung
- 1011 - 1024
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 21
Files
https://molmed.biomedcentral.com/counter/pdf/10.2119/molmed.2015.00098 https://europepmc.org/articles/PMC4982478?pdf=render
Datenquelle: Europe PubMed Central
- 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.
- Date of acceptance
- 2015
- Autoren
- 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
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/26650186
- DOI
- 10.2119/molmed.2015.00098
- eISSN
- 1528-3658
- Externe Identifier
- PubMed Central ID: PMC4982478
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Mol Med
- Sprache
- eng
- Country
- England
- Paginierung
- 1011 - 1024
- PII
- molmed.2015.00098
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Titel
- GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 21
Datenquelle: PubMed
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