Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases · 2004
[The role of signal transducer and activator of transcription-1 in the regulation of allergic airway inflammation in a guinea pig asthma model].
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Li Guo-ping, Xiong Ying, Liu Zhi-gang, Zhong Nan-shan
Аннотация
OBJECTIVE: To study the expression of signal transducer and activator of transcription-1 (STAT-1), and to investigate the effect and mechanism of STAT-1 on airway inflammation.
METHODS: Forty-eight guinea pigs were divided randomly into control group (group A, n = 8), asthma group (group B) and prevention group (group C, n = 8). The guinea pigs in group B were subdivided randomly into groups B(1), B(2), B(3) and B(4) (each n = 8). Asthma guinea pig models in group B and group C were set up by intraperitoneal injection and nebulization aspiration of ovalbumin (OVA). Expression levels of epithelial STAT-1 and intercellular adhesion molecule-1 (ICAM-1) were detected by immunohistochemistry, and lung tissue extracts were analyzed for phosphorylation of STAT-1 by western blot. Total cell and eosinophil (EOS) counts were examined, and expression levels of interferon-gamma (INF-gamma) were measured by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage (BAL).
RESULTS: After challenge, the expression levels of epithelial STAT-1 [(57 +/- 9), (136 +/- 14), (95 +/- 21), (67 +/- 30), respectively] and ICMA-1 [(75 +/- 10), (166 +/- 17), (113 +/- 14), (87 +/- 21), respectively] in groups B(1 - 4) were significantly different from those in group A [(13 +/- 7), (21 +/- 8), P < 0.01]. The expression levels of epithelial STAT-1 (25 +/- 7) and ICMA-1 (29 +/- 11) in group C were also significantly different from those in group B(4) (P < 0.01). The phosphorylation of STAT-1 was found in lung extracts from groups B(1 - 3). The dynamic changes of STAT-1 was correlated with that of EOS counts, and a positive correlation being observed (r = 0.652, P < 0.01). There was a significant correlation between epithelial STAT-1 and ICAM-1 (r = 0.556, P < 0.001). A negative correlation was found between epithelial levels of the STAT-1 and levels of INF-gamma in BALF (r = -0.499, P < 0.05) from group B(1 - 4).
CONCLUSION: Epithelial STAT-1 showed constitutive activation and excess expression in guinea pig asthma models, which was significantly correlated with airway inflammation, suggesting that STAT-1 may play an important role in airway inflammation and asthma treatment.
METHODS: Forty-eight guinea pigs were divided randomly into control group (group A, n = 8), asthma group (group B) and prevention group (group C, n = 8). The guinea pigs in group B were subdivided randomly into groups B(1), B(2), B(3) and B(4) (each n = 8). Asthma guinea pig models in group B and group C were set up by intraperitoneal injection and nebulization aspiration of ovalbumin (OVA). Expression levels of epithelial STAT-1 and intercellular adhesion molecule-1 (ICAM-1) were detected by immunohistochemistry, and lung tissue extracts were analyzed for phosphorylation of STAT-1 by western blot. Total cell and eosinophil (EOS) counts were examined, and expression levels of interferon-gamma (INF-gamma) were measured by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage (BAL).
RESULTS: After challenge, the expression levels of epithelial STAT-1 [(57 +/- 9), (136 +/- 14), (95 +/- 21), (67 +/- 30), respectively] and ICMA-1 [(75 +/- 10), (166 +/- 17), (113 +/- 14), (87 +/- 21), respectively] in groups B(1 - 4) were significantly different from those in group A [(13 +/- 7), (21 +/- 8), P < 0.01]. The expression levels of epithelial STAT-1 (25 +/- 7) and ICMA-1 (29 +/- 11) in group C were also significantly different from those in group B(4) (P < 0.01). The phosphorylation of STAT-1 was found in lung extracts from groups B(1 - 3). The dynamic changes of STAT-1 was correlated with that of EOS counts, and a positive correlation being observed (r = 0.652, P < 0.01). There was a significant correlation between epithelial STAT-1 and ICAM-1 (r = 0.556, P < 0.001). A negative correlation was found between epithelial levels of the STAT-1 and levels of INF-gamma in BALF (r = -0.499, P < 0.05) from group B(1 - 4).
CONCLUSION: Epithelial STAT-1 showed constitutive activation and excess expression in guinea pig asthma models, which was significantly correlated with airway inflammation, suggesting that STAT-1 may play an important role in airway inflammation and asthma treatment.