TSLP Promotes Lung Inflammation In Asthmatic Patients

Objectives:Allergic asthma is a allergic disease induced by many factors,characterized by airway hyperresponsiveness and airway chronic inflammation.The nature of asthma is a chronic inflammatory disorder of the airway in which many cells and cellular elements play a role, characterized by Infiltration of many inflammatory cells such as eosinophils (EOS), mast cells, T lymphocytes, etc.The morbidity and mortality of asthma are increasing year by year, It’s very serious to public health, its main etiology and pathogenesis is very complex, it is one of the hot spot in the research by many countries in the world.A long-recognized property of airway epithelial cells is their function as a complex physical barrier that defends against exposures to potentially harmful inhaled substances and microbial pathogens. The airway epithelium is not only a physical barrier, but also plays a key role in initiating, maintaining, and regulating inherent immunity and adaptive immunoreactions. A functional imbalance of Thl/Th2leukocytes mediated by dendritic cells(DC) is an important mechanism in asthma as the overabundance of Th2cells induces eosinophilic inflammation of the bronchial airway.Thymic stromal lymphopoietin (TSLP) is a cytokine secreted by airway epithelium, and recent studies indicated that TSLP expression was higher in asthma patients than healthy controls[4,5]. There are specific TSLP-receptors (TSLPRs) on the surfaces of dendritic cells (DCs). Binding of TSLP to TSLPR activates DCs and initiates the expression of CD40, CD80, and CD86. This simultaneous overexpression of CD40, CD80, and CD86may promote differentiation of ThO cells Th2cells that release inflammatory cytokines. These cytokines can further exacerbate airway inflammation [6] We measured the expression of TSLP in the airway epithelium of asthma patients to investigate the contribution of TSLP signaling to the pathogenesis of asthma and the mechanisms through which TSLP promotes airway inflammation.Methods:The asthma group was composited by10asthmatic patients, and the control group was composited by10healthy patients. Two groups of researchers have done lung function testing. Sputum smears stained with HE. Observed the expression of TSLP on the bronchial brush by Fluorescence immune dyeing method. Thymic stromal lymphopoietin in the alveolar lavage fluid and the serum levels of TSLP, IL-4, IL-5, and IL-13were detected by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. Flow cytometric detection of CD40, CD80, and CD86surface expression in PBMCs.The date of the asthma group would be reaserched one more time by the above methods,after inhaling Seretide (50/250) for one month. Statistic analysis:Results were analyzed using the SPSS10.0software package. All data were expressed as x-±s. Paired treatment mean were compared by independent samples t-tests. A.P<0.05was the threshold for statistical significance.Results:1. Initial patient conditions There was no significant difference in age between the asthma group and the control group (P>0.05). While the average forced expiratory volume in1s (FEV1) and the FEV1%of the asthma group were not significantly different from controls (P>0.05), FEV1/FVC%, peak expiratory flow (PEF), and PEF%were all significantly lower in asthmatic patients (FEV1/FVC%, P<0.01; PEF, P<0.001; PEF%, P<0.001)(Table1).2. Sputum smears stained with HE In the asthmatic patients, sputum samples contained many eosinophils, while few were observed in sputum samples from the control group (Figure1).3. Expression of TSLP in the airway epithelium Bronchial epithelial cells were weakly positive for TSLP in control patients but intensely stained in tissue samples from the asthma group (Fig.2).4. Expression of TSLP in BALF and the level of cytokines in plasma The concentration of TSLP in BALF was also significantly higher in the asthma group (p<0.05)(Table3). Similarly, serum levels of TSLP, IL-4, IL-5, and IL-13were all significantly higher in the asthma group (p<0.01).5. Surface expression of CD40, CD80, and CD86in PBMCs Compared to the control group, the surface expression of CD40, CD80, and CD86was enhanced in PBMCs from asthma patients as measured by flow cytometry (P<0.01)(Table4, Figure3).6. Seretide treatment Reduced expression of TSLP would decrease the activation of dendritic cells and the release of Th2cytokines. After inhaling Seretide (50/250) for one month, the expression of TSLP in the EA was in fact markedly reduced, along with PBMC surface expression of CD40, CD80and CD86, and the serum levels of TSLP, IL-4, IL-5and IL-13(Tables2-4).Conclusions:1. TSLP was highly expressed in epithelial cells of the airway in mice with asthma.2. TSLP can aggravate asthmatic lung inflammation by activating DCs to promote Th2differentiation.3. The expression of TSLP in the EA was in fact markedly reduced, along with activation of DCs, and the serum levels of Cytokines. TSLP signaling is crucial for generation of an inflammatory reaction in asthma.