Involvement of bone marrow-derived fibrocyte in the pathogenesis of pulmonary fibrosis and the effect of newly developed anti-fibrotic agents

骨髓源性纤维细胞在特发性肺纤维化的发病机制中起重要作用。吡非尼酮（PFD）是一种抗纤维化药物;然而，尚未研究其对纤维细胞的影响。本研究的目的是调查PFD是否抑制博莱霉素（BLM）处理小鼠肺中纤维细胞池的大小。为了实现这一点，用BLM处理C57 BL/6小鼠并施用PFD。在BLM处理的小鼠肺中的纤维细胞池的大小被PFD减弱。在治疗环境中也观察到了这一点。在BLM处理的小鼠肺中增加的趋化因子（CC基序）配体-2（CCL 2）和CCL 12的产生被PFD显著减弱。在体外，PFD可显著抑制纤维细胞向CCL 2的迁移和纤维细胞上趋化因子受体（CC基序）的表达。纤维细胞抑制被认为是PFD抗纤维化作用的机制。

Bone marrow-derived fibrocytes reportedly play important roles in the pathogenesis of idiopathic pulmonary fibrosis. Pirfenidone (PFD) is an anti-fibrotic agent; however, its effects on fibrocytes have not been investigated. The aim of this study was to investigate whether PFD inhibits fibrocyte pool size in the lungs of bleomycin (BLM)-treated mice. To achieve this, C57BL/6 mice were treated with BLM and PFD was administered. Fibrocyte pool size in BLM-treated mice lungs was attenuated by PFD. This was also observed in a therapeutic setting. Increased chemokine (CC motif) ligand-2 (CCL2) and CCL12 production in BLM-treated mouse lungs was significantly attenuated by PFD. Fibrocyte migration toward CCL2 and chemokine (CC motif) receptor-2 expression on fibrocytes were significantly inhibited by PFD in vitro. Fibrocyte inhibition is considered a mechanism of anti-fibrotic action of PFD.