Women's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Immunology Group, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48103, USA.
Mediators Inflamm. 2018 Jan 24;2018:7934362. doi: 10.1155/2018/7934362. eCollection 2018.
Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both and studies demonstrated that Gr-1TRAIL bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts. Although soluble TRAIL was increased in plasma from IPF patients, the presence of TRAIL myeloid cells was markedly reduced in IPF lung biopsies, and primary lung fibroblasts from this patient group expressed little of the TRAIL receptor-2 (DR5) when compared with appropriate normal samples. IL-13 was a potent inhibitor of DR5 expression in normal fibroblasts. Together, these results identified TRAIL myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF.
特发性肺纤维化（IPF）是最常见的间质性肺疾病形式，其特征为持续存在激活的肌成纤维细胞，导致细胞外基质蛋白过度沉积和深刻的组织重塑。在本研究中，肿瘤坏死因子相关凋亡诱导配体（TRAIL）的表达是博来霉素诱导的肺纤维化消退的关键。 和 研究均表明，Gr-1TRAIL 骨髓源性髓样细胞可阻止肺肌成纤维细胞的激活。尽管 IPF 患者的血浆中可溶性 TRAIL 增加，但在 IPF 肺活检中，TRAIL 髓样细胞明显减少，与适当的正常样本相比，该患者组的原代肺成纤维细胞表达的 TRAIL 受体-2（DR5）很少。IL-13 是正常成纤维细胞中 DR5 表达的有效抑制剂。综上所述，这些结果表明 TRAIL 髓样细胞是肺纤维化消退的关键机制，靶向促进其功能的策略可能在 IPF 中有治疗潜力。
