STAT1 activation and STAT1-dependent immune-response gene ICAM-1 expression in alveolar macrophages of rats suffered from interstitial pulmonary fibrosis.
OBJECTIVE
To investigate the role of signal transducer and activator of transcription 1(STAT(1)) in alveolar macrophages (AMs) from rats with bleomycin-induced pulmonary fibrosis.


METHODS
Fifty adult female Wistar rats were randomly divided into two groups: One group was intratracheally instilled with bleomycin (BLM), while another group with 9 g/L NaCl solution (NS). The kinetic change of STAT(1) activation and intercellular adhesion molecule-1(ICAM-1) expression in AMs was examined by Western blot and immunohistochemical staining, respectively.


RESULTS
(1)STAT(1) was rarely activated in AMs of NS group. After bleomycin treatment, the STAT(1) activation of AMs was significantly increased on day 1, climaxed on day 7, and then gradually decreased, but remaining significantly higher than that of NS group on day 28 (P<0.05). (2)There was only a few cells ICAM-1 higher than that positively stained in AMs of NS group. After intratracheal instillation of bleomycin, the number of ICAM-1 positive stained cells was significantly increased on day 1, reached its peak values on day 7, and then gradually decreased, and still higher than that of NS group on day 28 (P<0.05).(3)There was a significant correlationship between STAT(1) activation and ICAM-1 expression in AMs (r =0.913, P<0.01). Further more, the ICAM-1 expression in AMs was significantly correlated with the severity of inflammation in lung tissues (r =0.947, P<0.01).


CONCLUSIONS
STAT(1) was abnormally activated in AMs of rats with bleomycin-induced interstitial pulmonary fibrosis (IPF). The abnormal STAT(1) activation may play a role in the pathogenesis of acute alveolitis and pulmonary fibrosis.
Fan
Xian-ming
XM
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041,China.
Wang
Zeng-li
ZL
Li
Zhen-hua
ZH
D000818:Animals; D001761:Bleomycin; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor / Q000378:metabolism*
D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1