Expression of protease-activated receptors in allergic fungal rhinosinusitis

Int Forum Allergy Rhinol. 2014 Apr;4(4):266-71. doi: 10.1002/alr.21295. Epub 2014 Feb 5.

Abstract

Background: The etiology of the intense inflammatory response showed by patients with allergic fungal rhinosinusitis (AFRS) remains a mystery. Potential sources of this inflammation may include fungal proteases. Protease-activated receptors (PARs) are components of the innate immune response that are modulated by proteolytic activity and are involved in potentiating T helper 2 (Th2) responses. The objective of the study was to determine whether there is differential expression of PARs in patients with AFRS compared to controls.

Methods: The study was designed as a comparison of gene expression profiles in patients with AFRS vs diseased and nondiseased controls. Twenty-five patients were enrolled. Patients with AFRS (n = 15) were compared to nondiseased controls (n = 5) undergoing minimally invasive pituitary surgery (MIPS) and patients with chronic rhinosinusitis with nasal polyps (CRSwNP, n = 5) undergoing functional endoscopic sinus surgery (FESS). Ethmoid mucosa RNA was hybridized to 4 × 44 K microarray chips. Four gene probes (PAR1, PAR2, PAR3, and PAR4) were used to assess for differential expression. A linear-mixed model was used to account for some patients having multiple samples. Significance level was determined at p < 0.05.

Results: Of the 4 probes, only PAR3 showed statistically significant differential expression between AFRS and nondiseased control samples (p = 0.03) as well as a 2.21-fold change. No additional statistical difference in PAR expression among the comparison groups was noted.

Conclusion: PARs have been shown to enhance production of inflammatory cytokines and potentiate Th2 responses. In this initial report, patients with AFRS have a significantly increased expression of PAR3 compared to nondiseased controls.

Keywords: allergic; fungal rhinosinusitis; polyps; protease; receptors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycoses / genetics*
  • Mycoses / microbiology
  • Nasal Polyps / genetics*
  • Nasal Polyps / microbiology
  • Receptors, Proteinase-Activated / genetics*
  • Rhinitis, Allergic
  • Rhinitis, Allergic, Perennial / genetics*
  • Rhinitis, Allergic, Perennial / microbiology
  • Sinusitis / genetics*
  • Sinusitis / microbiology
  • Young Adult

Substances

  • Receptors, Proteinase-Activated