Aerosolized STAT1 antisense oligodeoxynucleotides decrease the concentrations of inflammatory mediators in bronchoalveolar lavage fluid in bleomycin-induced rat pulmonary fibrosis

被引：29

作者：

Zeng, Ming ^{[1
]}

Liao, Bin ^{[2
]}

Zhu, Chen ^{[1
]}

Wang, Wenjun ^{[1
]}

Zhan, Xiaoqin ^{[1
]}

Fan, Xianming ^{[1
]}

机构：

[1] Luzhou Med Coll, Affiliated Hosp, Dept Resp Med, Luzhou 646000, Peoples R China

[2] Luzhou Med Coll, Affiliated Hosp, Dept Cardiothorac Surg, Luzhou 646000, Peoples R China

来源：

CELLULAR & MOLECULAR IMMUNOLOGY | 2008年 / 5卷 / 03期

基金：

中国国家自然科学基金;

关键词：

pulmonary fibrosis; STAT1; ASON; aerosolization; inflammatory mediator;

D O I：

10.1038/cmi.2008.27

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

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 TG 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.

引用

页码：219 / 224

页数：6

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