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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(10): 1301-1307, 2017 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-29070458

RESUMO

OBJECTIVE: To explore the role of the receptor for advanced glycation end products (RAGE) in regulating the expression of MUC5AC and mucus production in a mouse model of toluene diisocyanate (TDI)?induced asthma. METHODS: BALB/c mice were randomly divided into control group, vehicle (AOO) group, TDI?induced asthma group and RAGE inhibitor (FPS?ZM1) group. PAS staining, Western blotting, and immunohistochemistry were used to analyze the changes in mucus production and MUC5AC expression in the airway of the mice, and the expression of p?ERK was detected with Western blotting. In vitro cultured human bronchial epithelial cell line 16HBE was transfected with lentiviral vector carrying short hairpin RNA targeting RAGE (shRNA?RAGE) and subsequently challenged with a TDI?human serum albumin (TDI-HSA) conjugate, and the changes in cellular MUC5AC mRNA expression as detected using RT-PCR; the protein expressions of ERK and p?ERK in the cells were examined with Western blotting. The effect of ERK inhibitor U0126 pretreatment on MUC5AC mRNA expression was also analyzed in the cells. RESULTS: Compared with the control mice, TDI-induced asthmatic mice showed significantly higher rates of PAS positivity and increased MUC5AC and p?ERK expressions in the airway (P<0.05). Treatment with FPS?ZM1 significantly decreased PAS positivity and lowered MUC5AC and p?ERK expressions in the airway of the asthmatic mice (P<0.05). Exposure of 16HBE cells to TDI?HSA caused a significant increase in MUC5AC mRNA expression and p?ERK protein expression (P<0.05), while RAGE knockdown obviously suppressed TDI?HSA-induced upregulation of p-ERK and MUC5AC mRNA (P<0.05). Treatment with the ERK inhibitor U0126 also lowered TDI?HSA?induced up?regulation of MUC5AC mRNA in the cells (P<0.05). CONCLUSION: RAGE signaling induces MUC5AC expression via extracellular signal-regulated kinase pathway to promote mucus overproduction in mice with TDI-induced asthma.


Assuntos
Asma/metabolismo , Mucina-5AC/metabolismo , Muco/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Asma/induzido quimicamente , Benzamidas/farmacologia , Butadienos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos BALB C , Nitrilas/farmacologia , Distribuição Aleatória , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Tolueno 2,4-Di-Isocianato
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(7): 932-5, 2016 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-27435771

RESUMO

OBJECTIVE: To evaluate fractional exhaled nitric oxide (FENO) level in patients with subacute cough and its value in predicting the patients' response to inhaled corticosteroids (ICS) treatment. METHODS: A total of 100 patients with persistent cough lasting more than 3 weeks were enrolled, including 52 patients with subacute cough and 48 with chronic cough. FENO, spirometry, and responses to ICS therapy of the patients were evaluated. RESULTS: The recruited patients had a median (inter-quartile ranges) FENO level of 19 ppb (12-30 ppb). Patients with chronic cough had a significantly higher median FENO level than those with subacute cough (20.5 vs 16 ppb; Z=-2.245, P=0.025). A FENO level ≥25 ppb was recorded in 15 (28.8%) patients with subacute cough, as compared with 20 (41.6%) in patients with chronic cough (χ(2)=1.801, P=0.179). With a FENO ≥25 ppb as the critical value to justify ICS treatment, 15 patients with subacute cough received ICS and 14 (93.3%) of them showed obvious relief of cough after 2 weeks of therapy, a response rate similar to that of 85.0% (17/20) in patients with chronic cough receiving the treatment (χ(2)=0.588, P=0.443). In patients with subacute cough, those with cough variant asthma (CVA) or eosinophilic bronchitis (EB) had a significantly higher median FENO level than those with postinfectious cough [(16 (11-31) ppb vs 11 (8-19) ppb, P<0.01]. In the etiological analysis, CVA or EB was identified in 23 (44.2%) of the patients with subacute cough, as compared 21 (43.8%) in patients with chronic cough (χ(2)=0.002, P=0.961). CONCLUSION: FENO may be an important indicator for etiological diagnosis of subacute cough and for predicting the response to ICS treatment.


Assuntos
Corticosteroides/uso terapêutico , Tosse/tratamento farmacológico , Óxido Nítrico/análise , Testes Respiratórios , Doença Crônica , Tosse/diagnóstico , Expiração , Feminino , Humanos , Masculino
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