Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice

• Published in: Respiratory research Vol. 14; no. 1; p. 101
• Main Authors: Liu, Wei, Wan, Jing, Han, Jian-Zhong, Li, Chen, Feng, Dan-Dan, Yue, Shao-Jie, Huang, Yan-Hong, Chen, Yi, Cheng, Qing-Mei, Li, Yang, Luo, Zi-Qiang
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.10.2013; BioMed Central
• Subjects: Animal models; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Bleomycin; Bleomycin - adverse effects; Cell Proliferation - drug effects; Collagen; Cytokines; Disease Models, Animal; Dosage and administration; Drug therapy; Fibroblasts - drug effects; Hydroxyproline - metabolism; In Vitro Techniques; Inflammation; Interleukin-1beta - metabolism; Interleukins; Kinases; Lung - metabolism; Lung - pathology; Lungs; Male; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Patient outcomes; Peptide Fragments - pharmacology; Peptide Fragments - therapeutic use; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - prevention & control; Risk factors; Rodents; Transforming Growth Factor beta1 - pharmacology; Treatment Outcome; Tumor Necrosis Factor-alpha - metabolism; Uteroglobin - pharmacology; Uteroglobin - therapeutic use; China
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-14-101

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. 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. 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. 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.