Mucosal mast cells respond to both IgE-dependent (antigen) Vadimezan ic50 and non-IgE-dependent (bacterial toxins, neurotransmitters, etc.) stimulation and release a wide variety of bioactive mediators into adjacent tissues and exert their function in the allergic inflammation and in modulation of the gut function [9]. Besides an increased vascular permeability, mucosal oedema and contraction of smooth muscles, a diminished barrier integrity

was observed leading to an antigen-induced enhanced epithelial permeability [10]. These activated mast cells produce Th2-type cytokines, such as IL-3, IL-5 and IL-13 leading to the accumulation of eosinophils and other inflammatory cells relevant to allergic diseases [11]. The importance of calcium influx in mast cell activation and degranulation has been well recognized [12]. The degranulation of mast cell is Ca2+ dependent, and an increase in intracellular Ca2+ characterized by Ca2+ entry through store-operated calcium channels (SOCs) is essential for granule release [13-15]. Multiple mechanisms are involved in regulation of SOCs activity. It has recently been discovered that the two subunits, STIM1 and Orai1, play a vital role in both the signalling and the permeation mechanisms for Ca2+ influx through Crenolanib solubility dmso SOCs. Overexpression of STIM1 together with Orai1 caused a

dramatic increase in store-operated Ca2+ entry in RBL cells [16]. Furthermore, SOC activation has been suggested to be linked to PI-3K signalling pathways, as well as reactive oxygen species (ROS) production, despite controversial. However, whether food allergen–induced mast cell activation is related to the regulation of intracellular Ca2+ signalling, and the underlying mechanism remain unknown. In this study, using Brown-Norway rat food-allergic model, we aimed to investigate the involvement of Ca2+ signalling in food allergen–induced

mast cell activation and degranulation and the underlying mechanisms. We found that Ca2+ entry through SOCs was increased in mast cells in the food-allergic animal model. SOC activation was related to PI3K-ROS-induced upregulation of STIM1 and Orai1 expression. Four-week-old female Brown-Norway rats were purchased from Vital old River Laboratories (Beijing, China) and housed in groups of four per cage in a controlled environment with a photoperiod of 12-h light/12-h dark and a temperature of 20 ± 2 °C. Sanitary controls were performed for all major rodent pathogens, and the results of these tests were uniformly negative. All the animal experimental procedures were approved by the Animal Care and Use Committee of Shenzhen University and carried out in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication no. 85-23, revised 1996). Forty Brown-Norway rats were randomly divided into two groups: control group and ovalbumin (OVA, Sigma, USA) group.