Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice

Respiratory Research

Zi-Qiang Luo¹  Yang Li¹  Qing-Mei Cheng¹  Yi Chen¹  Yan-Hong Huang¹  Shao-Jie Yue²  Dan-Dan Feng¹  Chen Li³  Jian-Zhong Han¹  Jing Wan¹  Wei Liu¹ 

[1] Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha 410078, PR China;Department of Pediatrics, Xiangya Hospital of Central South University, Changsha 410008, PR China;Department of Physiology, ChangZhi Medical College, Changzhi 046000, PR China

关键词: Uteroglobin receptor;    Antiflammin-1;    Pulmonary fibrosis;    Bleomycin;   

Others  :  792670
DOI  :  10.1186/1465-9921-14-101

 received in 2013-07-20, accepted in 2013-10-03,  发布年份 2013

【 摘 要 】

Background

Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a synthetic nonapeptide with diverse biological functions. In the present study, we investigated whether AF-1 has a protective effect against bleomycin-induced pulmonary fibrosis.

Methods

C57BL/6 mice were injected with bleomycin intratracheally to create an animal model of bleomycin-induced pulmonary fibrosis. On Day 7 and Day 28, we examined the anti-inflammatory effect and antifibrotic effect, respectively, of AF-1 on the bleomycin-treated mice. The effects of AF-1 on the transforming growth factor-beta 1 (TGF-β1)-induced proliferation of murine lung fibroblasts (NIH3T3) were examined by a bromodeoxycytidine (BrdU) incorporation assay and cell cycle analysis.

Results

Severe lung inflammation and fibrosis were observed in the bleomycin-treated mice on Day 7 and Day 28, respectively. Administration of AF-1 significantly reduced the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the lung homogenates on Day 7. Histological examination revealed that AF-1 markedly reduced the number of infiltrating cells on Day 7 and attenuated the collagen deposition and destruction of lung architecture on Day 28. The hydroxyproline (HYP) content was significantly decreased in the AF-1-treated mice. In vitro, AF-1 inhibited the TGF-β1-induced proliferation of NIH3T3 cells, which was mediated by the UG receptor.

Conclusions

AF-1 has anti-inflammatory and antifibrotic actions in bleomycin-induced lung injury. We propose that the antifibrotic effect of AF-1 might be related to its suppression of fibroblast growth in bleomycin-treated lungs and that AF-1 has potential as a new therapeutic tool for pulmonary fibrosis.

【 授权许可】

   
2013 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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