[The role of signal transducer and activator of transcription-1 in the regulation of allergic airway inflammation in a guinea pig asthma model].
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).


CONCLUSIONS
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.
Li
Guo-ping
GP
Department of Respiratory Diseases, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
Xiong
Ying
Y
Liu
Zhi-gang
ZG
Zhong
Nan-shan
NS
D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000378:metabolism*
D050794:STAT1 Transcription Factor; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone