Liang Olin D, Kleibrink Bjoern E, Schuette-Nuetgen Katharina, Khatwa Umakanth U, Mfarrej Bechara, Subramaniam Meera
Department of Medicine, Division of Respiratory Diseases, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
Exp Lung Res. 2011 Sep;37(7):435-44. doi: 10.3109/01902148.2011.584359. Epub 2011 Jul 25.
Lung transplantation has the worst outcome compared to all solid organ transplants due to chronic rejection known as obliterative bronchiolitis (OB). Pathogenesis of OB is a complex interplay of alloimmune-dependent and -independent factors, which leads to the development of inflammation, fibrosis, and airway obliteration that have been resistant to therapy. The alloimmune-independent inflammatory pathway has been the recent focus in the pathogenesis of rejection, suggesting that targeting this may offer therapeutic benefits. As a potent anti-inflammatory agent, epigallo-catechin-galleate (EGCG), a green tea catechin, has been very effective in ameliorating inflammation in a variety of diseases, providing the rationale for its use in this study in a murine heterotopic tracheal allograft model of OB. Mice treated with EGCG had reduced inflammation, with significantly less neutrophil and macrophage infiltration and significantly reduced fibrosis. On further investigation into the mechanisms, inflammatory cytokines keratinocyte (KC), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α), involved in neutrophil recruitment, were reduced in the EGCG-treated mice. In addition, monocyte chemokine monocyte chemoattractant protein-1 (MCP-1) was significantly reduced by EGCG treatment. Antifibrotic cytokine interferon-γ-inducible protein-10 (IP-10) was increased and profibrotic cytokine transforming growth factor-β (TGF-β) was reduced, further characterizing the antifibrotic effects of EGCG. These findings suggest that EGCG has great potential in ameliorating the development of obliterative airway disease.
与所有实体器官移植相比,肺移植的预后最差,这是由于存在被称为闭塞性细支气管炎(OB)的慢性排斥反应。OB的发病机制是同种免疫依赖性和非依赖性因素的复杂相互作用,这会导致炎症、纤维化和气道闭塞的发展,而这些情况对治疗具有抵抗性。同种免疫非依赖性炎症途径是近期排斥反应发病机制的研究重点,这表明针对该途径可能具有治疗益处。作为一种强效抗炎剂,表没食子儿茶素没食子酸酯(EGCG),一种绿茶儿茶素,在改善多种疾病的炎症方面非常有效,这为其在本研究的OB小鼠异位气管同种异体移植模型中的应用提供了理论依据。用EGCG治疗的小鼠炎症减轻,中性粒细胞和巨噬细胞浸润明显减少,纤维化也显著减轻。在对机制的进一步研究中,参与中性粒细胞募集的炎症细胞因子角质形成细胞(KC)、白细胞介素-17(IL-17)和肿瘤坏死因子-α(TNF-α)在EGCG治疗的小鼠中减少。此外,EGCG治疗可显著降低单核细胞趋化因子单核细胞趋化蛋白-1(MCP-1)。抗纤维化细胞因子干扰素-γ诱导蛋白-10(IP-10)增加,促纤维化细胞因子转化生长因子-β(TGF-β)减少,进一步证实了EGCG的抗纤维化作用。这些发现表明,EGCG在改善闭塞性气道疾病的发展方面具有巨大潜力。