To explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood mononuclear cells (PBMCs) and its relationship with pulmonary ventilation function in asthmatic patients, 18 asthmatic patients and 18 healthy subjects were selected. HO-1 protein and mRNA levels in PBMCs were measured by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Blood carbon monoxide Hb (COHb), serum total IgE and pulmonary ventilatory function were observed. Our results showed that the percentage of cells positive for immunohistochemical staining of HO-1 were significantly higher in asthmatic patients (41.72 +/- 7.44) % than that in with healthy subjects (10.45 +/- 4.36) % (P < 0.001) and the optical density of PBMC HO-1 mRNA was higher in asthmatic patients (26.05 +/- 4.14) than that in healthy subjects (10. 82 +/- 4.26) (P < 0.001). The relation analysis showed that PBMC HO-1 protein and mRNA levels had significantly negative relation with FEV1%, PEFR, MEFR50%, respectively (r = -0.51-0.89, P < 0.05-0.001, respectively) and a positive relation with COHb and serum total IgE (r = 0.48-0. 85, 0.05-0.001, respectively). It is concluded that the expression of PBMC HO-1 protein and mRNA increased significantly in asthmatic patients, and HO-1 may play a significant role in the pathogenesis of asthma. The expression of HO-1 may bear a relation with severity of asthma.
Asthma/blood ; Asthma/*enzymology ; Carbon Monoxide/blood ; Heme Oxygenase-1/*biosynthesis ; Heme Oxygenase-1/blood ; Immunoglobulin E/*blood ; Leukocytes, Mononuclear/*enzymology ; RNA, Messenger/blood

OBJECTIVE15-lipoxygenase (15-LO) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Gene expression profiling studies show the association between 15-LO and allergic asthma. This study was designed to observe the expression of 15-LO in lungs of asthmatic rats and examine the effects of dexamethasone on 15-lipoxygenase expression.

METHODSTwenty-seven male Sprague-Dawley (SD) rats were randomly divided into three groups: control, asthma and dexamethasone (DXM) intervention. An asthma model was prepared by sensitization and challenging with ovalbumin. The production of 15-LO in lung tissue homogenates was measured using ELISA.The expression of 15-LO mRNA in lungs was determined by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSThe levels of 15-LO mRNA and protein in the asthma group (0.51 ± 0.14 and 2080 ± 73 μg/mL, respectively) were lower than those in the control group (0.76 ± 0.15 and 2472 ± 106 μg/mL, respectively; P<0.01). DXM intervention increased significantly the levels of 15-LO mRNA and protein (1.02 ± 0.34 and 2562 ± 218 μg/mL) compared with the asthma group (P<0.01).

CONCLUSIONSThe production of 15-LO in lung tissues is reduced in asthmatic rats. DXM can increase the expression of 15-LO in lung tissues and thus might provide anti-inflammatory effects in asthmatic rats.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Arachidonate 15-Lipoxygenase ; analysis ; genetics ; Asthma ; drug therapy ; enzymology ; Dexamethasone ; pharmacology ; Lung ; enzymology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

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

OBJECTIVETo study the expression of heme oxygenase-1 (HO-1) gene and protein and the effect of budesonide (BUD) on the HO-1 expression in lung tissues in rats with asthma.

METHODSFifty male Sprague-Dawley rats were randomly divided into 5 groups: normal control, asthma model, dexamethasone (DXM)-, hemin (HO-1 challenger)-or BUD-treated asthma. The asthma model was prepared by ovalbumin sensitization and challenge. The rats were sacrificed 24 hrs after the last challenge. The blood COHb content,and the total cell count and the percentage of differential cells in bronchoalveolar lavage fluid (BALF) were measured. The expression of HO-1 protein and mRNA in lung tissues was detected with immunohistochemistry and RT-PCR, respectively. The airway inflammation situations were evaluated by histopathology.

RESULTSThe airway inflammatory cell infiltration in the DXM-, hemin- and BUD-treated asthma groups was remarkably alleviated compared with that in the asthma model group. Compared with the normal control group, the expression of HO-1 mRNA and protein in lung tissues and the blood COHb content in the asthma model and the DXM-, hemin- and BUD-treated asthma groups were significantly up-regulated. The DXM-, hemin- and BUD-treated asthma groups showed significantly increased expression of HO-1 protein and mRNA in lung tissues compared with the asthma model group. The blood COHb content in the DXM-and the hemin-treated asthma groups was significantly higher than that in the asthma model group.

CONCLUSIONSThe expression of HO-1 protein and mRNA in lung tissues and blood HO-1 activity increased in rats with asthma,suggesting that HO-1 may be involved in the pathogenesis of asthma. HO-1 may have a protective effect against the airway inflammation in asthmatic rats. BUD and DXM can up-regulate the expression of HO-1 protein and mRNA, thus providing protective effects against the airway inflammation in asthmatic rats.

Animals ; Asthma ; drug therapy ; enzymology ; Budesonide ; pharmacology ; therapeutic use ; Carboxyhemoglobin ; analysis ; Dexamethasone ; pharmacology ; Heme Oxygenase-1 ; analysis ; genetics ; Hemin ; pharmacology ; Lung ; enzymology ; Male ; RNA, Messenger ; analysis ; Random Allocation ; Rats ; Rats, Sprague-Dawley

1-Alkyl-2-acetylglycerophosphocholine Esterase ; blood ; genetics ; Adolescent ; Asthma ; blood ; enzymology ; genetics ; Child ; Child, Preschool ; Female ; Gene Expression Regulation, Enzymologic ; Genotype ; Humans ; Infant ; Male ; Mutation ; Polymerase Chain Reaction

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

OBJECTIVETo observe the clinical efficacy of treating chronic persistent bronchial asthma (CPBA) children with abnormal myocardial enzyme spectrum (AMES) by Yupingfeng Powder (YP) combined routine therapy.

METHODSFrom January 2010 to December 2012, 156 CPBA children patients with AMES were randomly assigned to the treatment group (80 cases) and the control group (76 cases). All patients received routine treatment (inhaled corticosteroids and/or leukotriene regulator). Besides, those in the treatment group took YP. The treatment duration was 3 months. The scores of children asthma control test (C-ACT), pulmonary function (FEV,% and PEF%), myocardial enzyme spectrum were observed before and after treatment, and 3 months before and after treatment. The myocardial enzyme spectrum of 40 healthy children at the baby clinics during the same period were recruited as the control.

RESULTSCompared with the control group, creatine kinase isoenzyme (CK-MB), creatine kinase(CK), and lactate dehydrogenase (LDH) increased in the two treatment groups (P <0.01), but there was no statistical difference in AST (P >0.05). Compared with before treatment in the same group, CK-MB, CK, LDH, and AST decreased in the treatment group after treatment and 3 months after treatment (P <0.01). CK-MB, CK, LDH, and AST decreased in the control group 3 months after treatment (P <0.01, P <0.05).Compared with after treatment, CK decreased in the control group 3 months after treatment (P <0.01). C-ACT score, FEV(1),%, and PEF% all increased in the two groups after treatment and 3 months after treatment (P <0.01, P <0.05). Compared with after treatment in the same group, CK decreased in the control group 3 months after treatment (P <0. 01). Compared with the control group in the same period, post-treatment CK-MB and CK decreased (P <0. 01, P <0. 05), while post-treatment C-ACT score, FEV, %, and PEF% increased (P <0.05) in the treatment group (P <0.05).

CONCLUSIONYP could strengthen specific and non-specific immunity of the organism, and improve clinical symptoms and the level of myocardial enzyme spectrum.

Asthma ; therapy ; Child ; Chronic Disease ; therapy ; Creatine Kinase, MB Form ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Myocardium ; enzymology

OBJECTIVETo study the effects of alltrans retinoic acid (ATRA) on airway responsiveness, airway remodeling and expression of matrix metalloproteinase-9 (MMP-9) protein in rats with asthma.

METHODSForty rats were randomly divided into five groups: asthma model, normal saline (control), ATRA treatment, cotton oil treatment and budesonide treatment (n=8 each). Asthma was induced by ovalbumin sensitization and challenge in the asthma model, and the ATRA, cotton oil or budesonide treatment groups. ATRA (50 μg/kg), cotton oil (1 mL) or budesonide (0.32 mg/kg) was administered before ovalbumin challenge in the three treatment groups. Airway responsiveness was assessed. The lung tissues were sampled to detect airway remodeling and the expression of MMP-9 protein by immunohistochemistry.

RESULTSThe expression of MMP-9 in lung tissues in the ATRA treatment group was significantly higher than that in the control group, but the airway responsiveness in the ATRA treatment group was not significantly different from that in the control group. The airway responsiveness and the expression of MMP-9 in lung tissues were significantly reduced in the ATRA treatment group compared with the asthma model group. The airway remodeling was significantly improved in the ATRA treatment group compared with the asthma model group.

CONCLUSIONSATRA may alleviate airway hyperresponsiveness and airway remodeling possibly through decreasing the protein expression of MMP-9 in rats with asthma.

Airway Remodeling ; drug effects ; Animals ; Asthma ; drug therapy ; pathology ; physiopathology ; Bronchi ; drug effects ; pathology ; physiopathology ; Lung ; enzymology ; Matrix Metalloproteinase 9 ; analysis ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology

OBJECTIVETo observe the expression of protein arginine N-methyltransferase (PRMT) genes in the lung and spleen of E3 rats with acute asthma.

METHODSE3 rats with ovalbumin-induced pulmonary inflammation were divided into two groups (n=10), and the validity of the acute asthma model was evaluated by histological observation with HE and PAS staining and by measurement of NO production. Semi-quantitative RT-PCR was employed to detect the expressions of PRMT1-PRMT6 genes in the lung and spleen tissues of the rats.

RESULTSIn the lung tissue of the asthmatic rats, the gene expressions of PRMT1 (P<0.01), PRMT2 (P<0.01), PRMT3 (P<0.05) and PRMT5 (P<0.05) were significantly increased, but the expression of PRMT4 gene (P<0.05) was significantly decreased as compared with those in the control tissue. In the spleen tissue of the asthmatic rats, the expressions of PRMT2 (P<0.05) and PRMT5 genes (P<0.05) showed a significant increase as compared with those in the control rat tissue.

CONCLUSIONThe gene expressions of PRMTs vary significantly between asthmatic rats and control rats, suggesting that PRMTs play an important role in the post-translational modification process of asthma-related genes.

Acute Disease ; Animals ; Asthma ; enzymology ; Female ; Male ; Protein Processing, Post-Translational ; Protein-Arginine N-Methyltransferases ; classification ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Inbred Strains

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