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Proinflammatory mediators alter expression of nuclear factor kappa B-regulating deubiquitinases in sinonasal

Ping Li1, Ying Wang2, Justin H Turner1

  • 1Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University School of Medicine, Nashville, TN.

International Forum of Allergy & Rhinology
|April 25, 2015
PubMed
Abstract

Insights

Nuclear factor κB (NF-κB) regulating deubiquitinases A20, Cezanne, and CYLD are present in sinonasal tissue. These enzymes are differentially regulated by inflammatory signals, suggesting a role in mucosal immunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Otolaryngology

Background:

  • Nuclear factor κB (NF-κB) is a key transcription factor in inflammatory responses.
  • NF-κB activity is regulated by deubiquitinating enzymes (A20, Cezanne, CYLD) in a negative-feedback loop to prevent chronic inflammation.
  • Understanding these regulators in the sinonasal epithelium is crucial for mucosal immunity.

Purpose of the Study:

  • To characterize the expression of NF-κB-regulating deubiquitinases (A20, Cezanne, CYLD) in the sinonasal epithelium.
  • To investigate the functional role of these deubiquitinases in response to inflammatory stimuli.

Main Methods:

  • Immunohistochemistry was used to assess deubiquitinase expression in normal sinonasal tissue.
  • Cultured sinonasal epithelial cells (SNECs) were stimulated with cytokines (TNF-α, IL-4, IL-13) and LPS.
  • Western blots and qRT-PCR were employed to measure NF-κB activation and deubiquitinase expression changes.

Main Results:

  • NF-κB activation was observed in response to LPS and TNF-α, but not IL-4 or IL-13.
  • A20, Cezanne, and CYLD were expressed in the sinonasal epithelium, mainly on the apical surface.
  • Proinflammatory mediators differentially affected A20 expression, with upregulation by LPS/TNF-α and downregulation by IL-4/IL-13.

Conclusions:

  • NF-κB-regulating deubiquitinases A20, Cezanne, and CYLD are expressed in sinonasal tissue.
  • These enzymes are differentially induced by inflammatory cytokines and LPS.
  • Results indicate a significant role for these deubiquitinases in sinonasal mucosal immunity and homeostasis.
Keywords:
A20CYLDCezanneNF-κBTNFAIP3deubiquitinaseepithelial cellinflammationrhinosinusitissinonasal

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