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The Research On The Effect Of Chemokines CXCL13 In Bronchial Asthma

Posted on:2018-10-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:C H WangFull Text:PDF
GTID:1314330542483463Subject:Geriatrics
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BackgroundBronchial asthma is an allergic airway disease,the development of asthma conveys a variety of cytokine cells,such as T cells,eosinophils,mast cells,B cells,basophils and other pathogenesis.Activation of airway inflammatory cells leads to the release of inflammatory mediators and inflammatory cytokines,leading to inflammatory cell infiltration,contraction of airway smooth muscle,increased vascular permeability,and mucus secretion and airway remodeling.The moving and interaction of these inflamatory cells is modulated by a group of biological active matters,and we call these chemokines.Chemokines are a family of small proteins,have a common structural motif,and are produced by several immune and non-immune cell types in response to damage,allergens,antigens,or microorganisms.Chemokines are recognized by receptors with seven transmembranal domains(7TM)coupled to G-proteins,and their biological activity is in concentrations as low as 1–100 ng/ml,they play an significant role in recruitment and cell activation of both leukocytes and resident cells at the allergic inflammatory site via their receptors.Trafficking and recruitment of cell populations with specific chemokines receptors assure the presence of reactive allergen-specific T-cells in the lung,and therefore the establishment of an allergic inflammatory process.CXCL13 was found in 1998 at first,it is one of the CXC chemokine family factors,also known as B cell-attracting chemokine 1,or B-lymphocyte chemoattractant.With the advent of Law of chemokines and their receptors naming system,due to its receptor CXC chemokine family and it was named CXCLl3.CXCL13 human gene is located at4q21,the homology of CXCL13 and other CXC chemokine family members is nearly24%-34%.CXCL13 was mainly produced by dendritic cells in lymphatic gland,spleen,Peyer's Patch and tonsil,human CXCL13 distributes mainly in liver,serum,lymph nodes and stomach,in addition,salivary glands and breast also have a small amount of it.It is reported that CXCL13 has been detected increased expression in a variety of autoimmune diseases,such as sinusitis,multiple sclerosis,optic neuritis,rheumatoid arthritis,Sjogren's syndrome,lupus nephritis,etc.,suggesting that CXCL13 is associated with allergy diseases and autoimmune diseases.Concerning the role of CXCL13 in bronchial asthma,Baby-Guzman confirmed the elevated expression of CXCL13 in the lung tissue derived from of OVA-challenged mice by PCR and immunohistochemical staining.Respectively,elevation of CXCL13 expression was associated with BALT formation and recruitment of both B cells and follicular CXCR5+ cells.Treating sensitized mice with anti-CXCL13 resulted in reduced airway inflammation.Furthermore,increased levels of CXCL13 were detected in BAL fluid derived from patients with asthma.However,expression of CXCL13 in serum of bronchial asthma patients and the relationship among it and IgE,eosinophils%,interleukin-6,interleukin-17 A have not yet been reported.Object1.Measure and compare the difference of serum CXCL13 level among acute exacerbation asthma patients,chronic persistent asthma patients and normal control subjects and analyse the relationship between serum CXCL13 level and the staging of bronchial asthma.2.Measure and compare the difference of serum IgE ?IL6?IL17A level among acute exacerbation asthma patients,chronic persistent asthma patients and normal control subjects,and analyse the correlation between serum CXCL13 level and these inflammatory markers levels in acute exacerbation asthma group,confirm therelationship between CXCL13 level and the inflammation level in acute exacerbation bronchial asthma.3.Measure and compare the difference of the eosinophils percentage in blood among acute exacerbation asthma patients,chronic persistent asthma patients and normal control subjects,and analyse the correlation between serum CXCL13 level and Eosinophil count in acute exacerbation asthma group,confirm the relationship between CXCL13 level and the inflammation level in acute exacerbation bronchial asthma.4.Measure and compare the difference of pulmonary function(FVC%,FEV1%,FEV1/FVC)in acute exacerbation asthma patients,chronic persistent asthma patients and normal control subjects,and analyse the correlation between serum CXCL13 level and pulmonary function in acute exacerbation asthma patients.Methods1.Clinical data collection,including gender,age,age of onset,duration,and acute episodes.2.Detected serum CXCL13,IgE,IL-6,IL-17 A levels of acute exacerbation asthma patients,chronic persistent asthma patients and normal control subjects by ELISA.3.Detected peripheral eosinophils count and percentage of acute exacerbation asthma patients,chronic persistent asthma patients and normal control subjects with Hemocytometer.4.Test research objects' lung function using Japan's HI-701 bedside lung function instrument.5.Operate data with SPSS 16.0 statistical analysis software,and analyse data with Mann–Whitney U test and Spearman's rank test.Consults1.Serum CXCL13 level was significantly higher in acute exacerbation groupSerum CXCL13 level in acute exacerbation group was significantly higher compared with that in chronic persistent group and normal control group,and serum CXCL13 level in chronic persistent group was significantly higher compared with that in normal control group.2.Serum IgE level was significantly higher in acute exacerbation groupHigher serum IgE level was found in acute exacerbation group compared with that in chronic persistent group and normal control group,and serum IgE level in chronic persistent group was significantly higher compared with that in normal control group.3.Serum IL-6 level was significantly higher in acute exacerbation groupHigher serum IL-6 level was found in acute exacerbation group compared with that in chronic persistent group and normal control group,while,there was no difference between serum IL-6 level in chronic persistent group and normal control group.4.There was no significant increase of IL-17 A level in serum of patients with bronchial asthmaThere was no difference between serum IL-17 A level in acute exacerbation group and that in chronic persistent group,the same result was found between acute exacerbation group and normal control group,chronic persistent group and normal control group.5.Eosinophil percentage in the blood was significantly higher in acute exacerbation groupEosinophil percentage in exacerbation group was significantly higher than that in chronic persistent group and normal control group,while,there was no difference between eosinophil percentage in chronic persistent group and normal control group.6.ventilatory functions declined in acute exacerbation groupLower FVC% was found in acute exacerbation group compared with that in chronic persistent group and normal control group,and FVC% in chronic persistent group was significantly lower compared with that in control group.Lower FEV1% wasfound in acute exacerbation group compared with that in chronic persistent group and normal control group,and FEV1% in chronic persistent group was significantly lower compared with that in normal control group.Lower FEV1/FVC was found in acute exacerbation group compared with that in chronic persistent group and normal control group,and FEV1/FVC in chronic persistent group was significantly lower compared with that in normal control group.7.The correlations among the level of CXCL13 and IgE,IL-6,IL-17 A,eosinophil percentage or different ventilatory functions in bronchial asthma patientsThere was positive correlation among the level of serum CXCL13 and the concentration of IgE,the level of IL-6 or IL-17 A,and the percentage of eosinophilic granulocytes in acute exacerbation bronchial asthma patients.Negative correlation was found between the level of CXCL13 and FVC%,or CXCL13 and FEV1% in acute exacerbation bronchial asthma patients.However,there was no significant correlation between the level of CXCL13 and FEV1//FVC.ConclusionSerum CXCL13 level in acute exacerbation group was significantly higher compared with that in chronic persistent group and normal control group,and there was positive correlation between the level of serum CXCL13 and the concentration of IgE,the level of IL-6 or IL-17 A,and the percentage of eosinophilic granulocytes,in acute exacerbation bronchial asthma patients,and negative correlation was found between the level of CXCL13 and FVC%,or CXCL13 and FEV1%.All of these support that CXCL13 plays an important role in the pathogenesis of bronchial asthma,and it can be used as a diagnostic indicator of acute exacerbation of bronchial asthma.
Keywords/Search Tags:CXCL13, chemokines, bronchial asthma, IgE, eosinophis
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