Mast cells play a key role in allergic and inflammatory reactions. Mast cells and some tumour cell lines such as RBL-2H3 express the high-affinity IgE receptor (FcεRI) on their cell surface. FcεRI is a member of the multichain immune recognition receptors (MIRRs), including T- and B-cell receptor. With regard to OVA-challenged and IgE-mediated mast cell degranulation, FcεRI aggregation activates phospholipase Cγ to increase IP3 generation. The IP3 selleck inhibitor causes Ca2+ release from the endoplasmic reticulum through IP3 receptors, which consequently

results in a large amount of Ca2+ influx via SOCs, leading to mast cell degranulation. In the present study, we demonstrated for the first time that parallel to enhancement of food allergen–induced mast cell degranulation, OVA-mediated Ca2+ entry through SOCs was increased. Given that increasing Ca2+ entry through SOCs enhances mast cell degranulation [20], we conclude that increase in Ca2+ entry through SOCs contributes to food allergen–mediated mast cell degranulation. The two membrane proteins, STIM1 and Orail, have been shown to be essential for the activation of SOCs [16]. Overexpression of Orai1 together with STIM1 has been suggested to upregulate Ca2+ entry through SOCs upon stimulation. In this study, we found that both mRNA and protein expressions levels of Orai1 and

STIM1 in mast cells were increased in OVA-sensitized animals, which is proposed to be an important reason accounting for the increase in SOC-mediated Ca2+ entry and mast cell activation. It has been suggested that the N-terminal Selleck Small molecule library of STIM1 is glycosylated and translocated from endoplasmic reticulum to the cell membrane when the calcium store is depleted, which process is

required for activation of SOCs [30]. This is in line with our study as the translocation of STIM1 protein to activated mast cell membrane in OVA-sensitized mast cells. Therefore, our study demonstrates for the first time that overexpression and activation of SOCs contributes to enhancement of Ca2+ entry through SOCs in food-allergic rats. Activated mast cell can release a diverse array of biologically active products, including preformed granule contents, the de novo synthesis of eicosanoids, Methocarbamol cytokines, chemokines and free radicals (such as ROS) [31]. Large amount of ROS has been demonstrated to generate in inflammatory cells during asthma, but little information is known in the situation of food allergy. A number of studies report that ROS are involved in the signals leading to degranulation and cytokine secretion in mast cells [32, 33]. In this study, we found that ROS production was significantly increased in the peritoneal lavage solution. Using Ebselen to partially scavenge ROS production (mainly hydrogen peroxide), Ca2+ entry through SOCs was inhibited.