The Effect Of Intervention Of Orail Pathway On Experimental Murine Allergic Rhinitis

Objectives:Orai1is the pore-forming subunit of the Ca2+ release-activated Ca2+ (CRAC) channels and plays a key role in the store-operated Ca2+ entry (SOCE). However, little is known about the function of this pathway in allergic rhinitis (AR). In this study we examined the expression of Orail and evaluated whether the intervention of Orai1 pathway was capable of controlling IgE-mediated allergic reactions by using AR mice models.Methods:AR models were established by repetitive intraperitoneal (i.p.) sensitization followed by intranasal (i.n.) challenge with ovalbumin to 24 BALB/c mice. We used immunohistochemical staining, western blotting and real-time reverse transcription-polymerase chain reaction (RT-PCR) to investigate Orai1 expression in nasal mucosa and nasal-associated lymphoid tissue (NALT) of normal, control and 2-aminoethoxydiphenyl borate (2-APB)-treated mice. In addition, we analyzed concentrations of nasal lavage fluid (NLF) leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin-specific IgE and interleukin-4 (IL-4) through enzyme-linked immunosorbent assay (ELISA), and measured mRNA levels of LTC4 synthase (LTC4S) and ECP in nasal mucosa, and germline Cεtranscription and IL-4 mRNA in NALT by using real-time RT-PCR among groups.Results:Orail was expressed in nasal mucosal epithelium, submucosal glands epithelium and immune system cells of NALT and was up-regulated remarkably in control mice.2-APB administration into the nostril markedly reduced numbers of sneezing and nasal rubbing as well as counts of invasive eosinophils in treated mice compared with that in control ones. Furthermore, the administration suppressed significantly Orai1 expression in nasal mucosa and NALT of treated mice compared to that of control ones. Similarly,2-APB treatment restrained remarkably NLF LTC4, ECP, ovalbumin-specific IgE and IL-4 and their corresponding mRNAs in above tissues of treated mice in comparison with those of control ones.Conclusions:Our results indicate that Orail exists in nasal mucosa and NALT, and 2-APB treatment effectively alleviates murine AR through pleiotropic activities.