[Expression of signal transducer and activator of transcription 6 in rat asthma model and the modulatory effect of dexamethasone].
OBJECTIVE
To study the expression of signal transducer and activator of transcription 6 and its mRNA in rat asthma model and the modulatory effect of dexamethasone (DXM).


METHODS
Thirty male SD rats were randomly divided into three groups: the control group, asthma group and DXM group. The rats in each group were sacrificed 24 h after the last challenge. In the experiment, the rat model of asthma was established by ovalbumin (OVA) challenge method. The lung tissue was taken from the left lung, and bronchoalveolar lavage fluid (BALF) was collected from the right lung. The total cell numbers, eosinophils (EOS) count and differentiated cell counts in BALF were performed on different count fluids. The concentrations of IL-4 in serum and BALF were measured by using sandwich ELISA. The protein expressions of STAT6 were detected with immunohistochemical techniques. The mRNA expressions of STAT6 were detected with in situ hybridization.


RESULTS
(1) The total cell counts in BALF, the absolute counts of EOS, and the ratios of eosinophils to the total cell numbers (EOS%) of asthma group were all significantly higher than those of the control group (P < 0.01). The total cell counts in BALF, the absolute counts of EOS, and EOS% of DXM group were all significantly lower than those of asthma group (P < 0.01). (2) The concentrations of IL-4 in BALF and serum of asthma group [(25.7 +/- 7.4) ng/L, (34.2 +/- 10.5) ng/L] were significantly higher than those of control group [(8.6 +/- 3.0) ng/L, (12.1 +/- 2.9) ng/L] (P < 0.01). The concentrations of IL-4 in BALF and serum of DXM group were significantly lower than those of asthma group. (3) Immunohistochemistry showed that the protein content of STAT6 around the bronchus of asthma group (0.171 +/- 0.025) was significantly higher than that of the control group (0.082 +/- 0.022) (P < 0.01), while that of DXM group (0.114 +/- 0.013) was significantly lower than that of asthma group. The epithelial cells were the cells. In situ hybridization showed that the mRNA expression of STAT6 around the bronchus of asthma group (0.180 +/- 0.013) was significantly higher than that of the control group (0.091 +/- 0.012) (P < 0.01), while that of DXM group (0.114 +/- 0.010) was significantly lower than that of asthma group. (4) There was a significant correlation between the concentration of IL-4 in BALF, the content of STAT6 and STAT6 mRNA, respectively, in the epithelial cells of bronchus. There was a significant correlation between the absolute numbers of EOS and EOS% in BALF, the content of STAT6 and STAT6 mRNA, respectively, in the epithelial cells of bronchus.


CONCLUSIONS
STAT6 protein and STAT6 mRNA were found strongly expressed in rat asthma model and the epithelial cells were the chief expressing cells. Dexamethasone had an inhibitory effect on airway inflammatory cells infiltration. It significantly depressed STAT6 and mRNA expression. Which may be a key process in modulatory mechanism of asthma.
Li
Chang-chong
CC
Department of Respiratory Medicine, Yuying Children's Hospital Affiliated to Wenzhou Medical College, Wenzhou 325027, China.
Ye
Le-ping
LP
Chen
Xiao-fang
XF
Li
Shao-bo
SB
Cai
Xiao-hong
XH
Dong
Lin
L
Luo
Yun-chun
YC
Zhang
Zheng-xia
ZX
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D003907:Dexamethasone