Interferon-α exerts proinflammatory properties in experimental radiation-induced esophagitis: Possible involvement of plasmacytoid dendritic cells
Interferon-α exerts proinflammatory properties in experimental radiation-induced esophagitis: Possible involvement of plasmacytoid dendritic cells
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DOI：
10.1016/j.lfs.2021.120215
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发表时间：
2021-12-16
期刊：
影响因子：
6.1
通讯作者：
Fujiwara, Yasuhiro
中科院分区：
文献类型：
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作者：
Kitamura, Hiroyuki;Tanigawa, Tetsuya;Fujiwara, Yasuhiro
目的：在肺癌和头颈癌的放射治疗期间经历的放射诱导的食管炎是治疗的主要剂量限制性副作用。本研究旨在阐明α-干扰素（IFN-α）在放射性食管炎中的作用。主要方法：C57 BL/6小鼠胸部单次照射10和25戈伊。照射后5天评估食管粘膜损伤和炎症反应。主要发现：辐射诱发的食管炎，其特征在于上皮层厚度减少，促炎细胞因子和趋化因子上调，炎性细胞浸润到食管粘膜中，以及上皮细胞凋亡。辐射上调了食管组织中IFN-α的基因表达水平，IFN-α中和抗体改善了辐射诱导的食管粘膜损伤，而IFN-α受体激动剂（RO 8191）的给药具有相反的作用。通过抗CD 317抗体或硼替佐米的药理学失活来消耗浆细胞样树突状细胞（pDC）抑制辐射诱导的粘膜炎症和损伤，伴随着IFN-α表达水平的降低。意义：这些发现表明IFN-α和pDC在放射诱导的食管炎的病理生理学中发挥促炎特性。
Aims: Radiation-induced esophagitis, experienced during radiation therapy for lung cancer and head and neck cancer, is a major dose-limiting side effect of the treatment. This study aimed to elucidate the role of interferon-alpha (IFN-alpha) in radiation-induced esophagitis. Main methods: C57BL/6 mice were exposed to 10 and 25 Gy of single thoracic irradiation. Esophageal mucosal damage and inflammatory reactions were assessed for 5 days after irradiation. Key findings: Irradiation induced esophagitis, characterized by reduction in the thickness of epithelial layer, upregulation of proinflammatory cytokines and chemokines, infiltration of inflammatory cells into the esophageal mucosa, and apoptosis of epithelial cells. Irradiation upregulated the level of gene expression for IFN-alpha in the esophageal tissue, and the neutralizing antibody against IFN-alpha ameliorated radiation-induced esophageal mucosal damage, while administration of IFN-alpha receptor agonist (RO8191) had an inverse effect. Depletion of plasmacytoid dendritic cells (pDCs) by anti-CD317 antibody or pharmacological inactivation with bortezomib suppressed radiation-induced mucosal inflammation and damage, accompanied by decrease in IFN-alpha expression level. Significance: These findings suggest that IFN-alpha and pDCs exert proinflammatory properties in the pathophysiology of radiation-induced esophagitis.