Suppression of connexin 26 is related to protease-activated receptor 2-mediated pathway in patients with allergic rhinitis

Am J Rhinol Allergy. 2012 Jan-Feb;26(1):e5-9. doi: 10.2500/ajra.2012.26.3740.

Abstract

Background: Connexin (Cx) 26 plays a key role in maintaining the integrity of tight junctions. However, the expression and modulation of Cx26 in allergic rhinitis (AR) has not been well understood.

Methods: We detected the expression of Cx26 in house-dust mite (HDM)-sensitized AR patients and investigated the Cx26 production and modulation in primary human nasal epithelial cells (HNECs) and BEAS-2B cells after treatment with the allergen Der p 1 from Dermatophagoides pteronyssinus.

Results: We found that the mRNA and protein levels of Cx26 were significantly down-regulated in AR patients compared with the control. Der p 1 was found to induce protease-activated receptor 2 (PAR2) expression and suppress Cx26 production significantly in vitro. PAR2 siRNA was shown to prevent the suppression of Cx26 induced by Der p 1 in BEAS-2B cells.

Conclusion: The suppression of Cx26 in HDM-sensitized AR patients is related to a PAR2-mediated pathway and might serve during the initiation and maintenance of AR. Targeting the PAR2-mediated Cx26 suppression may be a potential means of preventing allergic sensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, Dermatophagoides / immunology
  • Antigens, Dermatophagoides / pharmacology*
  • Arthropod Proteins / immunology
  • Arthropod Proteins / pharmacology*
  • Cells, Cultured
  • Connexin 26
  • Connexins / genetics
  • Connexins / immunology
  • Connexins / metabolism*
  • Cysteine Endopeptidases / immunology
  • Cysteine Endopeptidases / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Humans
  • Male
  • Middle Aged
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism*
  • Nasal Mucosa / pathology
  • Nasal Polyps / etiology
  • Nasal Polyps / metabolism
  • Pyroglyphidae
  • RNA, Small Interfering / genetics
  • Receptor, PAR-2 / genetics
  • Receptor, PAR-2 / immunology
  • Receptor, PAR-2 / metabolism*
  • Rhinitis, Allergic, Perennial / complications
  • Rhinitis, Allergic, Perennial / immunology*
  • Rhinitis, Allergic, Perennial / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Young Adult

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Connexins
  • GJB2 protein, human
  • RNA, Small Interfering
  • Receptor, PAR-2
  • Connexin 26
  • Cysteine Endopeptidases
  • Dermatophagoides pteronyssinus antigen p 1