Epigenetics of chronic rhinosinusitis and the role of the eosinophil

Kristin A. Seiberling, Christopher A. Church, Jason L. Herring, Lawrence C. Sowers

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: One theory for the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) involves aberration in the expression of genes that maintain the sinonasal innate immune system. We propose that the alteration in gene expression seen in CRSwNP is a result of oxidative byproducts of eosinophils. Activated eosinophils and neutrophils may lead to the production of hypobromous acid (HOBr) and hypochlorous acid (HOCL) and the posttranslational modification products 5-bromocytosine (5BrC) and 5-chlorocytosine (5ClC), respectively. 5BrC and 5ClC may cause aberrant methylation of cytosine during DNA replication and mimic the endogenous methylation signal associated with gene silencing. We propose to use gas chromatography-mass spectrometry (GC-MS) to identify the presence of 5BrC and 5ClC in CRSwNP patients. Methods: Patients with CRSwNP undergoing endoscopic sinus surgery were prospectively recruited into this study. Using GC-MS, tissue specimens were analyzed for the presence of 5BrC, 5ClC, and methylated cytosine. Results: Tissue specimens from 14 patients with CRSwNP and 3 normal controls were processed using GC-MS. CRSwNP specimens demonstrate elevated levels of 5BrC and 5ClC compared to normal controls. Conclusion: Eosinophils, which are predominantly found in CRSwNP, may lead to DNA modification and gene silencing via 5BrC and aberrant methylation patterns and may help explain the pathogenesis of CRSwNP.

Original languageEnglish (US)
Pages (from-to)80-84
Number of pages5
JournalInternational Forum of Allergy and Rhinology
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Bromocytosine
  • Chronic rhinosinusitis
  • Eosinophil
  • Epigenetics
  • Gene alteration
  • Innate immune system
  • Nasal polyps

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

Fingerprint Dive into the research topics of 'Epigenetics of chronic rhinosinusitis and the role of the eosinophil'. Together they form a unique fingerprint.

  • Cite this