Treatment with alpha-galactosylceramide attenuates the development of bleomycin-induced pulmonary fibrosis.
Treatment with alpha-galactosylceramide attenuates the development of bleomycin-induced pulmonary fibrosis.
复制标题
DOI：
--
复制
发表时间：
2004
影响因子：
4.4
通讯作者：
Toru Kimura;Yukio Ishii;Y. Morishima;A. Shibuya;K. Shibuya;M. Taniguchi;M. Mochizuki;A. Hegab;T. Sakamoto;A. Nomura;K. Sekizawa
中科院分区：
文献类型：
--
作者：
Toru Kimura;Yukio Ishii;Y. Morishima;A. Shibuya;K. Shibuya;M. Taniguchi;M. Mochizuki;A. Hegab;T. Sakamoto;A. Nomura;K. Sekizawa
肺纤维化是一种终末期疾病，目前尚无有效的治疗方法。尽管其发病机制尚不清楚，但肺纤维化是各种炎症的结果。NKT细胞调节炎症是因为它们能够通过糖脂配体的刺激产生大量细胞因子。在本研究中，我们研究了α -半乳糖神经酰胺（α - galcer），一种选择性NKT细胞配体，在博莱霉素诱导的肺纤维化发展中的作用。用α - galcer治疗小鼠，通过减轻肺纤维化的发展，延长了博来霉素给药小鼠的生存期。α - galcer的保护作用与肺中ifn - γ水平的增加和肺中纤维化细胞因子（如tgf - β和结缔组织生长因子）水平的降低有关。博来霉素引起的初始肺部炎症也随着巨噬细胞炎症蛋白-2水平的降低而被α - galcer减轻。在缺乏NKT细胞或抗ifn - γ Ab治疗的小鼠中，α - galcer的保护作用显着降低。这些结果表明，α - galcer抑制博莱霉素诱导的急性肺部炎症，从而可能通过调节几种细胞因子水平来减轻肺纤维化的发展。
Pulmonary fibrosis is an end-stage disorder for which efficacious therapeutic options are not readily available. Although its pathogenesis is poorly understood, pulmonary fibrosis occurs as a result of various inflammations. NKT cells modulate inflammation because of their ability to produce large amounts of cytokines by stimulation with their glycolipid ligand. In the present study, we investigated the effects of alpha-galactosylceramide (alpha-GalCer), a selective NKT cell ligand, on the development of bleomycin-induced pulmonary fibrosis. Treatment of mice with alpha-GalCer prolonged their survival under bleomycin administration by attenuating the development of pulmonary fibrosis. The protective effects of alpha-GalCer were associated with an increase in the pulmonary level of IFN-gamma and a decrease in the pulmonary level of fibrogenic cytokines such as TGF-beta and connective tissue growth factor. The initial pulmonary inflammation caused by bleomycin was also attenuated by alpha-GalCer with the reduction of the macrophage inflammatory protein-2 level. The protective effects of alpha-GalCer were markedly reduced in mice lacking NKT cells or as a result of treatment with anti-IFN-gamma Ab. These results suggest that alpha-GalCer suppresses bleomycin-induced acute pulmonary inflammation and thus attenuates the development of pulmonary fibrosis possibly by regulating several cytokine levels.