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首页> 外文期刊>Journal of dermatological science >Radiation-induced mast cell mediators differentially modulate chemokine release from dermal fibroblasts.
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Radiation-induced mast cell mediators differentially modulate chemokine release from dermal fibroblasts.

机译：辐射诱导的肥大细胞介质差异调节真皮成纤维细胞的趋化因子释放。

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摘要

BACKGROUND: Ionizing radiation has been demonstrated to result in degranulation of dermal mast cells. Chemokines are thought to play a crucial role in the early phase of the cutaneous radiation reaction. In human skin, mast cells are located in close proximity to dermal fibroblasts, which thus are a potential target for the action of mast cell mediators. OBJECTIVE: In this study, we evaluated the effects of mast cell-derived histamine, serotonin, tumour necrosis factor (TNF)-alpha and tryptase on chemokine release from dermal fibroblasts. METHODS: Human mast cells (HMC-1) were investigated for histamine release and cytokine production after ionizing radiation using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Receptor expression on human fetal foreskin fibroblasts (HFFF2) and human adult skin fibroblasts (HDFa) was examined by flow cytometry. Chemokine mRNA and protein expression were analyzed by gene array and ELISA, respectively. RESULTS: Ionizing radiation significantly increased histamine release and cytokine expression by HMC-1 cells. Receptors for histamine, serotonin, TNF-alpha and tryptase were detected both in HFFF2 and in HDFa cells. Dermal fibroblasts constitutively expressed distinct sets of chemokine mRNA. Mast cell mediators differentially affected the release of chemokines CCL8, CCL13, CXCL4 and CXCL6 by fibroblasts. CONCLUSIONS: Our data suggest that radiation-induced mast cell mediators have a tremendous impact on inflammatory cell recruitment into irradiated skin. We postulate the activation of mast cells to be an initial key event in the cutaneous radiation reaction, which might offer promising targets for treatment of both normal tissue side effects in radiation therapy and radiation injuries.
机译：背景：已证明电离辐射可导致真皮肥大细胞脱粒。人们认为趋化因子在皮肤辐射反应的早期阶段起着至关重要的作用。在人类皮肤中，肥大细胞紧邻真皮成纤维细胞，因此是肥大细胞介体作用的潜在靶标。目的：在这项研究中，我们评估了肥大细胞衍生的组胺，血清素，肿瘤坏死因子（TNF）-α和类胰蛋白酶对皮肤成纤维细胞释放趋化因子的影响。方法：采用酶联免疫吸附试验（ELISA）和流式细胞仪研究电离辐射后人肥大细胞（HMC-1）的组胺释放和细胞因子产生。通过流式细胞术检查了人类胎儿包皮成纤维细胞（HFFF2）和成人成年皮肤成纤维细胞（HDFa）上的受体表达。分别通过基因阵列和ELISA分析趋化因子的mRNA和蛋白表达。结果：电离辐射显着增加了HMC-1细胞的组胺释放和细胞因子表达。在HFFF2和HDFa细胞中均检测到组胺，5-羟色胺，TNF-α和类胰蛋白酶的受体。皮肤成纤维细胞组成性表达趋化因子mRNA的不同集合。肥大细胞介质差异化地影响成纤维细胞释放趋化因子CCL8，CCL13，CXCL4和CXCL6。结论：我们的数据表明，辐射诱导的肥大细胞介体对炎症细胞募集到受辐照皮肤中具有巨大影响。我们假设肥大细胞的激活是皮肤放射反应的最初关键事件，这可能为放射疗法中正常组织的副作用和放射损伤的治疗提供有希望的目标。

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