Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring.

Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring.
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辐照组织中细胞因子和生长因子表达的长期改变以及与组织学严重程度评分的关系。

DOI:
10.1371/journal.pone.0029399
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Dolivet G
Dolivet G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gallet P;Phulpin B;Merlin JL;Leroux A;Bravetti P;Mecellem H;Tran N;Dolivet G

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除了在癌症治疗中的功效外,放射治疗还会引起照射区域内健康组织的退化。本研究的目的是分析辐射引起的组织变性动物模型中促炎症(IL-1α、IL-2、IL-6、TNF-α、IFN-γ)、促纤维化(TGF-β1)、促血管生成(VEGF)和干细胞动员(GM-CSF)细胞因子和生长因子的变化。 24 只大鼠后肢单侧接受 30 Gy 剂量照射。照射后六周 (n = 8)、6 个月 (n = 8) 和 1 年 (n = 8) 使用蛋白质印迹和 Bio-Plex® 蛋白质阵列 (BPA) 技术分析皮肤和肌肉中的介质表达。根据组织学和免疫组织化学分析定义了纤维化、炎症、血管分布和细胞分布改变评分的其他组织学严重程度。在辐照组织中发现组织学严重程度评分显着增加。皮肤组织比肌肉对放射更敏感。在整个研究中发现了高水平的 TGF-β1 表达,并且证明了 TGF-β1 表达与纤维化评分之间存在显着关系。受照射的组织显示出慢性炎症(IL-2和TNF-α显着增加)。此外,在所有受辐射的组织中都发现了 GM-CSF 和 VEGF 的持续表达。血管评分与TGF-β1表达相关,细胞改变评分与IL-2、VEGF、GM-CSF水平显着相关。本研究取得的结果强调了放射诱导的细胞因子网络改变的复杂性和多样性。它提供了许多发展视角,用于理解晚期损伤的机制或对康复技术的作用方式和功效进行组织学和分子评估。
Beside its efficacy in cancer treatment, radiotherapy induces degeneration of healthy tissues within the irradiated area. The aim of this study was to analyze the variations of proinflammatory (IL-1α, IL-2, IL-6, TNF-α, IFN-γ), profibrotic (TGF-β1), proangiogneic (VEGF) and stem cell mobilizing (GM-CSF) cytokines and growth factors in an animal model of radiation-induced tissue degeneration. 24 rats were irradiated unilaterally on the hindlimb at a monodose of 30 Gy. Six weeks (n = 8), 6 months (n = 8) and 1 year (n = 8) after irradiation the mediators expression in skin and muscle were analyzed using Western blot and the Bio-Plex® protein array (BPA) technology. Additional histological severity for fibrosis, inflammation, vascularity and cellularity alterations scoring was defined from histology and immnunohistochemistry analyses. A significant increase of histological severity scoring was found in irradiated tissue. Skin tissues were more radio-sensitive than muscle. A high level of TGF-β1 expression was found throughout the study and a significant relation was evidenced between TGF-β1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-α significantly increased). Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-β1 expression and the cellular alterations score was significantly related with the level of IL-2, VEGF and GM-CSF. The results achieved in the present study underline the complexity and multiplicity of radio-induced alterations of cytokine network. It offers many perspectives of development, for the comprehension of the mechanisms of late injuries or for the histological and molecular evaluation of the mode of action and the efficacy of rehabilitation techniques.
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