Aerosolized STAT1 antisense oligodeoxynucleotides decrease the concentrations of inflammatory mediators in bronchoalveolar lavage fluid in bleomycin-induced rat pulmonary fibrosis.
It has been demonstrated that alveolar macrophages (AMs) play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators. In addition, abnormal signal transducer and activator of transcription-1 (STAT1) activation in AMs may play a pivotal role in the process of alveolitis and pulmonary fibrosis. In this study, we transfected STAT1 antisense oligodeoxynucleotide (ASON) into rats by aerosolization, and then investigated the effect of STAT1 ASON on inflammatory mediators such as TGF-beta, PDGF and TNF-alpha in bronchoalveolar lavage fluid (BALF) from rats with bleomycin (BLM)-induced rat pulmonary fibrosis. Our results showed that STAT1 ASON by aerosolization could enter into lung tissues and AMs. STAT1 ASON could inhibit mRNA and protein expressions of STAT1 and ICAM-1 in AMs of rat with pulmonary fibrosis, and had no toxic side effect on liver and kidney. Aerosolized STAT1 ASON could ameliorate the alveolitis through inhibiting the secretion of inflammatory mediators in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis.
Zeng
Ming
M
The Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, China.
Liao
Bin
B
Zhu
Chen
C
Wang
Wen Jun
WJ
Zhan
Xiao Qin
XQ
Fan
Xian Ming
XM
D000336:Aerosols; D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008081:Liposomes; D008168:Lung / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000336:Aerosols; D018836:Inflammation Mediators; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1