Centre for Rheumatology and Connective Tissue Diseases Research, Royal Free Hospital, UCL, Rowland Hill Street, London, NW3 2PF UK.
J Cell Commun Signal. 2010 Dec;4(4):187-8. doi: 10.1007/s12079-010-0100-4. Epub 2010 Oct 1.
Data from our laboratory show that in vitro fibroblasts are exquisitely responsive to prostacyclin and the prostacyclin derivative Iloprost, which block their activation by TGFβ. A recent article by Zhu Y et al confirm these effects in vivo showing that Iloprost, given as a single intraperitoneal injection, blocks lung fibrosis in the bleomycin model of lung injury and fibrosis. These results are important because at present no effective clinical treatments are available to treat idiopathic lung fibrosis, which progresses and leads to respiratory failure. Limiting factors for the clinical use of prostacyclin derivatives as anti-fibrotics are failure to achieve therapeutic levels in the involved fibrotic tissues, and dose limiting side effects due to vasodilatation and binding to the IP receptor on vascular cells. Possible approaches include fibroblast directed gene therapies or amelioration of the vascular side effects.
我们实验室的数据表明,体外成纤维细胞对前列环素和前列环素衍生物伊洛前列素非常敏感,这两种物质可以阻止它们被 TGFβ 激活。Zhu Y 等人最近的一篇文章在体内证实了这些效果,表明单次腹腔内注射伊洛前列素可以阻止博莱霉素诱导的肺损伤和纤维化模型中的肺纤维化。这些结果很重要,因为目前尚无有效的临床治疗方法可用于治疗特发性肺纤维化,这种疾病会进展并导致呼吸衰竭。作为抗纤维化药物,前列腺素衍生物的临床应用受到限制,原因是无法在涉及的纤维化组织中达到治疗水平,以及由于血管扩张和与血管细胞上的 IP 受体结合而导致的剂量限制的副作用。可能的方法包括针对成纤维细胞的基因治疗或改善血管副作用。