The Effects of Aerosolized STAT1 Antisense Oligodeoxynucleotides on Rat Pulmonary Fibrosis

• Published in: Cellular & molecular immunology Vol. 6; no. 1; pp. 51 - 59
• Main Authors: Wang, Wen Jun, Liao, Bin, Zeng, Ming, Zhu, Chen, Fan, Xian Ming
• Format: Journal Article
• Language: English
• Published: China Nature Publishing Group 01.02.2009; The Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China%The Department of Cardiothoracic Surgery, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China
• Subjects: Administration, Inhalation; Aerosols; Alveoli; Alveolitis; Animals; Antisense oligonucleotides; Bleomycin; Bleomycin - pharmacology; Bronchoalveolar Lavage Fluid; Collagen (type I); Collagen (type III); Collagen Type I - metabolism; Collagen Type III - metabolism; Female; Fibrosis; Hydroxyproline; Inflammation; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - metabolism; Liposomes - pharmacology; Lung - pathology; Lung diseases; Macrophages; Oligodeoxyribonucleotides, Antisense - genetics; Platelet-Derived Growth Factor - metabolism; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - pathology; Pulmonary Fibrosis - therapy; Rats; Rats, Wistar; Smad4 Protein - metabolism; STAT1; Stat1 protein; STAT1 Transcription Factor - antagonists & inhibitors; STAT1 Transcription Factor - genetics; Transforming Growth Factor beta - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; 反义寡核苷酸; 支气管肺泡灌洗液; 气雾化; 肺泡巨噬细胞; 肺间质纤维化; 胶原mRNA; inflammatory mediator; type Ⅰ and type Ⅲ collagen mRNA; STAT1; pulmonary fibrosis; ASON
• ISSN: 1672-7681; 2042-0226
• DOI: 10.1038/cmi.2009.7

Previous study showed that aerosolized signal transducer and activator of transcription-1 （STAT1） antisense oligodeoxynucleotide （ASON） inhibited the expression of STAT1 and ICAM-1 mRNA and protein in alveolar macrophages （AMs） and decreased the concentrations of TGF-β, PDGF and TNF-α in bronchioalveolar lavage fluid （BALF） in bleomycin （BLM）-induced rat pulmonary fibrosis. Administration of STAT1 ASON ameliorated alveolitis in rat pulmonary fibrosis. However, further investigations are needed to determine whether there is an effect from administration of STAT1 ASON on fibrosis. This study investigated the effect of aerosolized STAT1 ASON on the expressions of inflammatory mediators, hydroxyproline and type Ⅰ and type Ⅲcollagen mRNA in BLM-induced rat pulmonary fibrosis. The results showed that STAT1 ASON applied by aerosolization could ameliorate alveolitis and fibrosis, inhibit the expressions of inflammatory mediators, decrease the content of hydroxyproline, and suppress the expressions of type Ⅰand type Ⅲcollagen mRNA in lung tissue 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. Cellular ＆ Molecular Immunology.