Resarch On The Comprehensive Effect Of Bitter Taste Receptors On Chronic Airway Inflammation

Objective:To investigate the effects and related molecular mechanism of bitter taste receptor(TAS2Rs)on the development of chronic respiratory inflammation and mucus hypersecretion,expect to clarify its comprehensive therapeutic effect on chronic airway inflammatory diseases.Methods:This study was divided into two parts,and the rats were been used as the experimental object.Depending on the conditions of application,rats were divided into three groups,control group(inhalation with saline as negative control),experimental group(Establishment of rat model of chronic airway inflammation by PM2.5 inhalation stimulation),intervention group(inhalation ‘limonin’ extracted from Tangerine peel as an intervention factor on the basis of PM2.5).In the first: ELISA was used to determine the excretion levels of inflammatory cytokines TNF-α,IL-1β,IL-13 and CINC-1 in bronchoalveolar lavage fluid(BALF)of rats.RT-PCR and Western blot were used to detect the transcription and protein expression of inflammatory cytokines and the bitter taste receptor TAS2R14 in bronchus and lung tissue.And then: The expression of mucin MUC5 AC,MUC5B and TAS2R14 was detected by the same methods,and the effect of TAS2R14 on mucin synthesis and secretion was observed.Results:The effects of TAS2 Rs on correlative inflammatory cytokines in chronic airway inflammation:⑴ After PM2.5 inhalation,the m RNA and protein expression level of TNF-α,IL-1β,IL-13 and CINC-1 were significantly increased in bronchial/lung tissues and BALF of rats(P<0.01).⑵ After inhalation of ‘limonin’,the expression levels of m RNA and protein of TAS2R14 were significantly increased in bronchial/lung tissues(P<0.05).⑶ Compared with group PM2.5,the inflammatory cytokines TNF-α、IL-1β、IL-13 and CINC-1 in the intervention group were decreased both in transcription and protein expression levels(P<0.05).The effects of TAS2 Rs on mucus hypersecretion in chronic airway inflammation:⑴ After PM2.5 inhalation,the m RNA and protein expression of mucin MUC5 AC and MUC5 B in rat bronchial/lung tissues and BALF were increased(P<0.01,P<0.05),MUC5 AC increased more significantly.⑵ After ‘limonin’inhalation,the expression of TAS2R14 was increased while the m RNA and protein synthesis of mucin MUC5 AC and MUC5 B decreased in bronchial/lung tissues(P<0.05).However,the secretion expression of mucin MUC5 AC and MUC5 B in BALF was increased(P<0.05,P<0.01),and the expression of MUC5 B increased significantly.Conclusions:1.The stimulation of PM2.5 can induce chronic airway inflammation and mucus hypersecretion;2.The treatment of Chinese herbal medicine inhalation can inhibit the production and release of inflammatory cytokines in chronic inflammatory respiratory tract,and stimulate the expression of TAS2 Rs in the lung.The activation of TAS2 Rs in lung is an important mechanism of anti-inflammatory effect;3.Bitter Chinese medicine component inhalation can produce the dual effects of mucin production and the promotion of mucin secretion,which is achieved by activating the expression of TAS2 Rs in lung to enhance the anti-inflammatory effect of respiratory inflammation;4.Based on our research and the domestic and foreign research results,TAS2 Rs activation also produces a variety of beneficial effects,such as relaxing bronchus,increasing mucociliary clearance efficiency and inhibiting the colonization of pathogens.Thereby,TAS2 Rs has a comprehensive therapeutic effect on chronic airway inflammatory diseases.