[Effect of signal transducer and activator of transcription 1 antisense oligodeoxynucleotides on inflammatory mediators, type I and type III collagen mRNA of rat pulmonary fibrosis].
OBJECTIVE
To investigate the effect of aerosolized signal transducer and activator of transcription 1 (STAT1) antisense oligodeoxynucleotides (ASON) on the expression of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and typeI and typeIII collagen mRNA of the bleomycin-induced rat pulmonary fibrosis.


METHODS
45 adult female Wistar rats were randomly divided into 3 groups: normal saline (NS) group, bleomycin (BLM) group and ASON group. BLM group and ASON group were intratracheally instilled with bleomycin (BLM) while NS group was instilled with NS. NS group and BLM group were aerosolized with NS while ASON group was aerosolized with STAT1 ASON on day 0, 2, 4 and 6 after intratracheal administration. Then each group was divided into 3 subgroups and the rats were sacrificed on day 7, 14 and 28. The concentration of IFN-gamma, TNF-alpha, TGF-beta1 and PDGF-BB in BALF was detected. The lung tissues were removed and HE and Masson staining was performed to observe the extent of alveolitis and fibrosis. The mRNA levels of typeI and typeIII collagen in the lung tissues were measured.


RESULTS
Compared with BLM group, the scores of alveolitis and fibrosis in ASON group were remarkably meliorated (P<0.05). Compared with NS group, the concentration of TNF-alpha, TGF-beta1 and PDGF-BB in BALF in BLM group was significantly increased, but it was lower in ASON group than in BLMA group (P<0.05). The concentration of IFN-gamma in BALF was lower in BLM group than in NS group (P<0.05), but it was higher in ASON group than in BLM group (P<0.05). The mRNA levels of typeI and typeIII collagen at various time points in ASON group were significantly lower than those in BLM group (P<0.05).


CONCLUSIONS
The aerosolized STAT1 ASON has anti-fibrosis effect, which may result from the lessened production of typeI and typeIII collagen through reducing the concentration of cytokines in BALF such as TNF-alpha, PDGF-BB and TGF-beta1 and inhibiting the decline of IFN-gamma in BALF.
Wang
Wen-jun
WJ
Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, China. wangwenjun2005@163.com
Zeng
Ming
M
Liu
Dan
D
Fan
Xian-ming
XM
Zhu
Chen
C
Zhan
Xiao-qin
XQ
D000336:Aerosols; D000818:Animals; D000077214:Becaplermin; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D024042:Collagen Type I / Q000235:genetics*; D024061:Collagen Type III / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000336:Aerosols; D024042:Collagen Type I; D024061:Collagen Type III; D018836:Inflammation Mediators; D020319:Oligodeoxyribonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D000077214:Becaplermin; D007371:Interferon-gamma