Up-regulation of Orai1 in murine allergic rhinitis

Abstract

Orai1 is an essential pore-forming subunit of the Ca(2+) release-activated Ca(2+) channels and plays a key role in the store-operated Ca(2+) entry. However, little is known about the function of this pathway in allergic airway diseases. In this study, we evaluated Orai1 expression in normal and allergic rhinitis (AR) mice airway and spleen. AR models were established by repetitive intraperitoneal sensitization followed by intranasal challenge with ovalbumin. Sneezing was counted, and eosinophils infiltration was analyzed through Luna stain. We performed the analysis of Orai1 protein in airway and spleen by immunohistochemical staining, Western blotting and enzyme-linked immunosorbent assay, and quantitatively examined Orai1 mRNA in the above tissues by real-time reverse transcription-polymerase chain reaction. Sneezes and eosinophil counts in the AR group were increased in comparison to those in the normal group. Orai1 protein was expressed in mucosal epithelium and submucosal glands epithelium of airway, and in immune cells of spleen. The immunostaining appeared stronger in AR mice than that in normal ones. Both the Orai1 protein and mRNA levels showed up-regulation in the AR group compared with those in the normal one. Our results indicate that Orai1 is up-regulated in the airway and spleen in allergic inflammation and may participate in the pathogenesis of allergic rhinitis.

Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

“…Interestingly, contractions induced by Ca 2+ were higher in tissues obtained from OVA-challenged rats than from control animals, indicating that antigen challenge activated this phenomenon with a more pronounced participation of capacitative Ca 2+ entry into antigen-challenged tissues. Although a direct influence of antigen challenge on capacitative Ca 2+ entry has not been completely demonstrated hitherto, previous reports demonstrated the involvement of protein expression of store-operated Ca 2+ channels in allergic states (26)(27)(28). Sildenafil more evidently reduced the contractions induced by capacitative Ca 2+ entry in OVA-challenged tissues, and we suspect that it may alter the expression of genes related to the proteins of the TRPC subfamily, the so-called store-operated Ca 2+ channels (29).…”

Molecular modulation of airway epithelial ciliary response to sneezing

“…Chronic rhinosinusitis and allergic rhinitis are common diseases, with a 14 and 35% prevalence, respectively (6–8), that manifest with increased frequency of sneezing (9). In animal models of allergic rhinitis, induction of frequent sneezing is used to confirm establishment of allergic rhinitis (10). The functional effect of sneezing is to expel static or retained nasal respiratory secretions.…”

Histochemistry and cell biology: the annual review 2010

“…As immune system cell activation, proliferation and degranulation depend on Orai1 and involve calcineurin-/NFAT-signalling to express cytokine genes and other genes critical for the immune response, Lin et al (2010) investigated Orai1 expression in normal and allergic rhinitis (AR) mice airway and spleen. Orai1 protein was found in mucosal epithelium and submucosal glandular epithelium of airway, and in immune cells of spleen with higer expression in AR mice compared with wild-type mice.…”

“…The study by Lin et al (2010) focused on Orai1, the pore-forming subunit of Ca 2+ -release-activated Ca 2+ (CRAC) channels (Gwack et al 2007). As immune system cell activation, proliferation and degranulation depend on Orai1 and involve calcineurin-/NFAT-signalling to express cytokine genes and other genes critical for the immune response, Lin et al (2010) investigated Orai1 expression in normal and allergic rhinitis (AR) mice airway and spleen.…”