OBJECTIVETo evaluate the roles of various cytokines, histone acetyltransferase (HAT) and histone deacetylase (HDAC) in the pathogenesis of bronchial asthma.

METHODSBALB/C mice were randomly assigned to control, untreated asthma, hormone treatment and TSA treatment groups. Bronchial asthma was induced by intraperitoneal injections and atomization inhalation of ovalbumin (OVA) in the asthma, hormone treatment and trichostatin (TSA) treatment groups. The mice in the hormone treatment and TSA treatment groups were administered with dexamethasone 1.0 mg/kg and TSA 1.0 mg/kg respectively by an intraperitoneal injection 30 minutes before challenge of asthma. At 24 hours after the last challenge, IL-4, IL-8 and IFN- levels in serum were measured using ELISA, and activities of HAT and HDAC in peripheral blood mononuclear cells (PBMC) were determined by the enzyme linked immunofluorescence assay.

RESULTSThe serum levels of IL-4 and IL-8 in the untreated asthma group were higher than in the control, hormone treatment and TSA treatment groups (P<0.05). There was no difference in the serum levels of IL-4 and IL-8 among the control, hormone treatment and TSA treatment groups (P>0.05). The activity of HDAC in the untreated asthma group was lower than in the control, hormone treatment and TSA treatment groups (P<0.05). Hormone treatment significantly decreased the activity of HAT compared with the untreated asthma group (P<0.05). There was no difference in the activities of HAT and HDAC among the control, hormone treatment and TSA treatment groups (P>0.05).

CONCLUSIONSThe decreased activity of HDAC leads to an increased secretion of inflammatory factors and thus induces asthma.

Animals ; Asthma ; enzymology ; etiology ; immunology ; Cytokines ; blood ; Histone Acetyltransferases ; physiology ; Histone Deacetylases ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Th1 Cells ; immunology ; Th2 Cells ; immunology

Allergens ; immunology ; Animals ; Asthma ; etiology ; Enzyme Activation ; Lung ; pathology ; Matrix Metalloproteinases ; physiology ; Mice ; Respiratory Syncytial Virus Infections ; enzymology ; pathology

PURPOSE: A possible involvement of autoimmune mechanism in the pathogenesis of bronchial asthma has been proposed. Recently, alpha-enolase protein was identified as a major autoantigen recognized by circulating IgG autoantibodies in patients with severe asthma. To evaluate a possible pathogenetic significance of these autoantibodies in severe asthma, isotype (IgG, IgA, IgM, and IgE) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) distributions of autoantibodies to recombinant human alpha-enolase protein were analyzed. PATIENTS AND METHODS: We examined serum samples from 10 patients with severe asthma and 7 patients with mild-to-moderate asthma, and 5 healthy controls by immunoblot analysis. Severe asthma was defined as patients having at least 1 severe asthmatic exacerbation requiring an emergency department visit or admission in the last year despite continuous typical therapies. RESULTS: IgG1 was the predominant IgG subclass antibody response to alpha-enolase protein in patients with severe asthma. IgG1 autoantibody to alpha-enolase protein was detected in 7 of 10 patients with severe asthma (70%), 1 of 7 patients with mild-to-moderate asthma (14.3%), and none of 5 healthy controls (0%) (chi-square test; p < 0.05). IgA, IgM, and IgE autoantibodies to alpha-enolase protein could not be detected in patients with severe asthma. CONCLUSION: IgG1 subclass was the predominant type of autoantibody response to alpha-enolase protein in patients with severe asthma, suggests a possibility of IgG1 autoantibody- mediated complement activation in the pathogenesis of severe asthma.
Adult ; Aged ; Asthma/*enzymology/*immunology ; Autoantibodies/*blood/classification ; Autoantigens ; Case-Control Studies ; Complement Activation ; Female ; Humans ; Immunoglobulin G/blood/classification ; Immunoglobulin Isotypes/blood ; Male ; Middle Aged ; Phosphopyruvate Hydratase/*immunology ; Recombinant Proteins/immunology ; Young Adult

BACKGROUND/AIMS: We sought to increase our understanding of the rhinitis-asthma relationship and improve strategies for the treatment of patients with these diseases. The aim of this study was to identify a connection between upper airway inflammation and lower airway responsiveness. METHODS: We counted eosinophils on nasal smears, and performed spirometry, allergic skin tests, and methacholine challenge tests in 308 schoolchildren plus a questionnaire on respiratory symptoms. The methacholine concentration causing a 20% fall in forced expiratory volume in 1 second (PC20 < 25 mg/mL) was used as the threshold of bronchial hyperresponsiveness (BHR). RESULTS: In total, 26% of subjects had positive nasal eosinophils on a smear, and 46.2% of subjects had BHR at < 25 mg/mL methacholine PC20. Nasal symptoms were higher in subjects with than without nasal eosinophils (p = 0.012). Asthma symptoms did not differ between subjects with and without nasal eosinophils. Nasal eosinophils were higher in subjects with atopy than those without (p = 0.006), and there was no difference in PC20 methacholine according to atopy (15.5 +/- 1.07 vs. 17.5 +/- 0.62; p > 0.05). No difference in BHR was detected when comparing subjects with and without nasal eosinophils. There were significant differences in the PC20 between subjects with greater than 50% nasal eosinophils and without nasal eosinophils (11.01 +/- 2.92 mg/mL vs. 17.38 +/- 0.61 mg/mL; p < 0.001). CONCLUSIONS: These findings demonstrated that nasal eosinophilic inflammation might contribute to lower airway responsiveness in schoolchildren, based on an epidemiological survey.
Adolescent ; Age Distribution ; Age Factors ; Asthma/diagnosis/*epidemiology/physiopathology ; Bronchial Hyperreactivity/diagnosis/*enzymology/physiopathology ; Bronchial Provocation Tests ; Child ; Eosinophilia/diagnosis/*epidemiology/immunology ; Eosinophils/immunology ; Female ; Health Surveys ; Humans ; Intradermal Tests ; Leukocyte Count ; Lung/*physiopathology ; Male ; Nasal Mucosa/*immunology ; Republic of Korea/epidemiology ; Rhinitis/diagnosis/*epidemiology/immunology ; Spirometry ; Surveys and Questionnaires