Abstract
BackgroundAntiflammin-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.MethodsC57BL/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.ResultsSevere 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.ConclusionsAF-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.
Highlights
Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a synthetic nonapeptide with diverse biological functions
Our findings suggest that AF-1 has potential as a new therapeutic tool for pulmonary fibrosis
Time course of pulmonary fibrosis in bleomycin mouse model C57BL/6 mice were intratracheally injected with bleomycin (5 mg · kg-1) on Day 0
Summary
Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a synthetic nonapeptide with diverse biological functions. We investigated whether AF-1 has a protective effect against bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis is a progressive disorder characterized by the excessive proliferation of fibroblasts and deposition of extracellular matrix, which destroy normal tissue architecture and function. Clara cell secretory protein (CCSP) is mainly secreted from Clara cells. Lee and colleagues reported that UG knockout mice were extraordinarily sensitive to bleomycin and were highly susceptible to developing pulmonary fibrosis [8]. These results suggest that UG, as an endogenous protective factor, plays an important role in inhibiting pulmonary fibrosis
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