elizabeth f. redente, rebecca c. keith, william janssen, peter m. henson, luis a. ortiz, gregory p. downey, donna l. bratton, david w. h. riches
2014年4月27日讯 /生物谷bioon/--长期以来,炎症被认为在导致特发性肺纤维化中致命瘢痕形成的生物学过程中发挥重要作用但近日,national jewish health研究人员elizabeth redente博士和她的同事最新发现,在肺纤维化愈合和修复过程中,轻微炎症也可能是至关重要的相肺纤维化病能活多久关研究报告发表在american journal of respiratory cell and molecular biology杂志上,新研究揭示促炎细胞因子tnf-α可以加速受伤肺部恢复
炎症长期被认为是肺部疤痕的前体和原因,然而,抗炎治疗对于疾病进展并无积极效果近年来,一些研究人员认为,炎症可能是愈合以及肺部疤痕过程的一部分redente博士和她的同事在小鼠肺部已经受伤,产生疤痕组织后,给予小鼠tnf-α虽然这些老鼠肺损伤正常恢复,但研究人员发现,tnf-α能加速恢复过程
pmid:
炎症在疤痕发展中的作用近年来被热烈辩论,redente博士说:我们的研究结果第一次表明,在解除已经形成的疤痕肺纤维化能治愈吗过程中,tnf-α会真正促进炎症,轻微炎症在正确的位置和时间可能实际上是一件好事特发性肺纤维化患者一般在诊断后三年内死亡,每年约40,000名美国人死于特发性肺纤维化
tnf-α减少了胶原(瘢痕组织的主要成分)水平,并在自然恢复过程开始之前就能改善肺组织的自然愈合过程,研究人员还发现缺乏基因tnf-α基因敲除小鼠无法如野生型小鼠那样愈合
idiopathic pulmonary fibrosis (ipf) is a relentless, fibrotic parenchymal lung disease in which alternatively programmed macrophages produce 肺间质纤维化的治疗profibrotic molecules that promote myofibroblast survival and collagen synthesis. effective therapies to treat patients with ipf are lacking, and conventional therapy may be harmful. we tested the hypothesis that therapeutic lung delivery of the proinflammatory cytokine tumor necrosis factor (tnf)-α i肺间质纤维化症状nto wild-type fibrotic mice would reduce the profibrotic milieu and accelerate the resolution of established pulmonary fibrosis. fibrosis was assessed in bleomycin-instilled wild-type and tnf-α-/- mice by measuring hydroxyproline levels, static compliance, and masson’s trichrome staining. macrophage肺纤维化的治疗 infiltration and programming status was assessed by flow cytometry of enzymatically digested lung and in situ immunostaining. pulmonary delivery of tnf-α to wild-type mice with established pulmonary fibrosis was found to reduce their fibrotic burden, to improve lung function and architecture, and t肺纤维化治疗新方法o reduce the number and programming status of profibrotic alternatively programmed macrophages. in contrast, fibrosis and alternative macrophage programming were prolonged in bleomycin-instilled tnf-α-/- mice. to address the role of the reduced numbers of alternatively programmed macrophages in the 间质性肺炎tnf-α–induced resolution of established pulmonary fibrosis, we conditionally depleted macrophages in mafia (macrophage fas-induced apoptosis) mice. conditional macrophage depletion phenocopied the resolution of established pulmonary fibrosis observed after therapeutic tnf-α delivery. taken together, o肺纤维化还能活多久ur results show for the first time that tnf-α is involved in the resolution of established pulmonary fibrosis via a mechanism involving reduced numbers and programming status of profibrotic macrophages. we speculate that pulmonary delivery of tnf-α or augmenting its signaling pathway represent a nov特发性肺纤维化治疗el therapeutic strategy to resolve established pulmonary fibrosis.
pmc:
tumor necrosis factor-α accelerates the resolution of established pulmonary fibrosis in mice by targeting profibrotic lung macrophages.
doi:10.1165/rcmb.2013-0386oc
研究人员认为,tnf-α的作用是通过诱导巨噬细胞从促进纤维化的细胞变为促进炎症的细胞,tnf-α也可促进一些促纤维化巨噬细胞的死亡david riches博士表示肺纤维化可以治好吗:我们的研究结果表明,tnf-α不仅减缓了纤维化进程,实际上逆转肺部已经形成的疤痕北京公立白癜风医院
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