Effect of ethyl pyruvate on E-cadherin of airway epithelium in a TDI-induced mouse asthma / 实用医学杂志

Objective To explore the role of ethyl pyruvate (EP) on E-cadherin of airway epithelium and airway inflammation in a TDI-induced mouse asthma model. Methods 30 male BALB/c mice were randomly divided into control group , asthma group and EP group. On day 1 and 8 , mice in asthma group and EP group were treated with 0.3%TDI on the dorsum of both ears for sensitization. And on day 15 , 18 and 21 the mice underwent an aerosol inhalation of 3% TDI, and saline (100 mg/kg) was injected intraperitoneally 1 hour before inhalation. The control group underwent acetone and olive oil (AOO) sensitization on day 1 and 8, AOO challenge on day 15, 18 and 21. Saline (100 mg/kg) was injected intraperitoneally 1 hour before challenge. One hour before each challenge, mice were given EP (100mg/kg) or vehicle via intraperitoneal injection. On day 22, airway reactivity, IL-4 , IFN-γand IgE in the serum were detected , immunohistochemistry and WB were used to assess E-cadherin levels. Results Airway reactivity, IL-4, IFN-γin and IgE in the serum in asthma group are significantly higher than that in control group (P<0.05). Treatment with EP dramatically decreased airway hyperresponsiveness in TDI-challenged mice, as well as IL-4, IFN-γ and IgE (P < 0.05). E-cadherin in control group was distributed evenly at the connection of epithelial cells. E-cadherinin distribution was chaotic and its expression was decreased in asthma group. EP intervention can ameliorate the damage of E-cadherinin. Conclusions EP can ameliorate the destruction of E-cadherin in airway epithilum by TDI.

Expression of epidermal growth factor receptor (EGFR) and transforming growth factor beta1 (TGF beta1) in airway mucosa of toluene diisocyanate (TDI)-induced asthma patients / 천식및알레르기

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor(EGFR) and TGF beta1 have been known as a central regulator in airway remodeling. There have been some reports demonstrating expression of EGFR and TGF beta1 in airway mucosa of asthmatic patients. However, the expression of EGFR and TGF beta1 in bronchial epithelium of TDI-induced asthmatics has not been observed. The aim of this study was to observe expression of EGFR and TGF beta1 and evaluate their roles in pathogenic mechanism of TDI-induced asthma. METHODS: EGFR and TGF beta1 expression were compared using immunohistochemistry technique in bronchial mucosa from 22 subjects with TDI-induced asthma(group I: 10 newly diagnosed, group II: 12 TDI-induced asthma patients with persistent asthma symptoms for more than 5 years after diagnosis), 7 non-asthmatics undergoing pneumonectomy from lung tumor, and 3 healthy subjects. The intensity of expression was analyzed by two observers. The grade of intensity was presented from 0 to 3. Subepithelial basement membrane (SBM) thickness was measured using an image analyzer. RESULTS: EGFR expression was significantly higher in asthmatic patients than in wntrois (p>0.05), while no significant difference were nosed in TGF beta1 expression (p>0.05). There was no significant difference in EGFR expression between group I and II (p>0.05). However, grade of TGF beta1 expression was significantly higher in group II than those of group I (p0.05). CONCLUSION: These findings suggest that EGFR and TGF beta1 may contribute to pathogenesis of TDI-induced asthma. However, further studies are required to evaluate the role of EGFR and TGF beta1 in the pathogenesis of TDI-induced asthma.

Longitudinal study of specific antibodies to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate in patients with TDI-induced asthma

BACKGROUND: An appreciable number of patients with toluene diisocyanate (TDI)-induced asthma have high serum levels of specific IgE (sIgE) antibody to TDI-human serum albumin conjugate (HSA). A recent investigation suggested a role of specific IgG (sIgG) in the development of TDI asthma. METHODS: We observed the changes in the levels of specific IgE and IgG antibodies to TDIHSA conjugate in TDI-induced asthmatic patients during seven years avoidance. RESULTS: Six subjects with high sIgE and five with high sIgG were enrolled. All of them had taken anti-asthmatic medications with complete avoidance. Serum levels of sIgE and sIgG to TDI-HSA conjugate were detected by ELISA. The level of sIgE continued to decline up to 7 years and the mean half-life was 3.9 years. The mean half-life of sIgG was 4.5 yrs. CONCLUSION: These findings suggest that both sIgE and sIgG to TDI-HSA conjugate may persist for several years after the last exposure to TDI.

Localization of transforming growth factor beta1 in airway mucosa of toluene diisocyanate-induced asthma / 천식및알레르기

BACKGROUND AND OBJECTIVE: There have been some reports on the expression of TGF beta-an anti-inflammatory and fibrosing cytokine in airway mucosa of asthmatics. However, the ex- pression of TGF beta1 in bronchial mucosa of TDI-induced asthma is not known. The aim of this study was to observe immunolocalization of TGF beta1 in airway mucosa of TDI-induced asthma. METHODS: TGF beta1 expressions were compared using immunohistochemistry in bronchial muco- sa from 22 subjects with TDI-induced asthma (group I: 10 newly diagnosed, group II: 12 subjects with persistent asthma symptoms for more than 4 years after diagnosis), and 8 non- asthmatics undergoing pneumonectomy from lung tumor. The distribution and intensity of expression were analyzed by two observers in four areas of bronchial tissue-epithelium(EP), vascular endothelium(VE), smooth muscle(SM), and mucous glands(MG). RESULTS: Positive rates of TGF beta1 expression for groups I and II in the four areas were as follows; EP (50% vs 100%, p0.05). Grades of TGF beta1 expression of EP, VE, and SM were significantly higher in group II than in group I(p0.05, respectively). CONCLUSION: TGF beta1 expressions of EP, VE, SM and MG were noted in airway mucosa of TDI-induced asthma and expressions of EP, VE, and SM were more intense and frequent in patients with persistent asthma symptoms.

Expression of transforming growth factorbeta1 (TGFbeta1) and TGFbeta receptor II (R II) in airway mucosa of toluene diisocyanate (TDI)-induced asthma: relationships with persistent asthmatic symptoms / 대한내과학회지

BACKGROUND: The underlying mechanism to explain the poor prognosis of TDI-induced asthma is unknown. We performed this study to evaluate the role of TGFbeta1 and its receptor, TFGbeta receptor II (RII) in TDI-induced asthma. METHODS: We applied immunohistochemistry with monoclonal antibodies to TGFbeta1 and RII in bronchial mucosa from 22 subjects with TDI-induced asthma (group I: 10 newly diagnosed, group II: 12 subjects with persistent asthma symptoms for more than 4 years after diagnosis) and 8 non-asthmatics undergoing pneumonectomy from lung tumor. The expression was analyzed in 4 areas of bronchial tissue-epithelium (EP), vascular endothelium (VE), smooth muscle (SM), mucous gland (MG). The grade of intensity was presented from 0 to 3. Subepithelial basement memberane (SBM) and submucosal extracellular matrix (SECM) thickness were measured using an image analyzer. Serum specific IgE and IgG antibody levels to TDI- human serum albumin (HSA) conjugate were detected by ELISA. RESULTS: Grade of TGFbeta1 expression was significantly higher in EP, VE and SM in group II than those of group I of TDI-induced asthma (p0.05). Significant correlations were noted between asthma duration after diagonsis and intensity of TGFbeta1 expression in EP, VE and SM (p0.05). TGF 1 expression was significantly higher in EP, VE and SM in subjects with specific IgG antibody to TDI-HSA than those without it (p<0.05). CONCLUSION: These findings suggest that TGFbeta1 may contribute to develop persistent asthma symptoms in TDI-induced asthma.