Rhinosinusal Inflammation and High Mobility Group Box 1 Protein: A New Target for Therapy

ORL J Otorhinolaryngol Relat Spec. 2016;78(2):77-85. doi: 10.1159/000443481. Epub 2016 Mar 12.

Abstract

Background/aims: High mobility group box 1 (HMGB1) is a protein belonging to the class of damage-associated molecular pattern molecules, which activates innate immunity and powerful inflammatory factors. The aim of this review is to show the importance of HMGB1 in the pathogenesis of nasal inflammatory diseases and to suggest that inhibition of HMGB1 may be an innovative therapeutic target.

Methods: We used immunohistochemistry to study whether HMGB1 increases in chronic rhinosinusitis with nasal polyps and whether its expression is associated with eosinophils and inflammatory cytokines. Using primary cultures of human nasal epithelial cells, we localised lipopolysaccharide-induced active translocation and release of HMGB1 by immunofluorescence assay and Western blot.

Results: Patients with severe symptoms have the highest HMGB1 serum levels. Glycyrrhetic acid inhibits the chemotactic and mitogenic function of HMGB1, binding to the hydrophobic residues that delimit the pockets in box A and B.

Conclusions: Chronic inflammatory diseases of the nose and paranasal sinuses are increasingly prevalent and are a financial burden for society. HMGB1 has been shown to play a role in several inflammatory diseases of otolaryngological interest. The inhibition of HMGB1 may be an innovative therapeutic target for patients with chronic upper airway inflammatory diseases having nasal obstruction as a major symptom.

Publication types

  • Review

MeSH terms

  • Blotting, Western
  • Chronic Disease
  • DNA / genetics*
  • Gene Expression Regulation*
  • Genetic Therapy / methods*
  • HMGB1 Protein / biosynthesis
  • HMGB1 Protein / genetics*
  • Humans
  • Immunohistochemistry
  • Rhinitis / blood
  • Rhinitis / genetics*
  • Rhinitis / therapy
  • Sinusitis / blood
  • Sinusitis / genetics*
  • Sinusitis / therapy

Substances

  • HMGB1 Protein
  • DNA