Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
HLA Typing Laboratory, Blood Center of Wuhan, Wuhan, China.
Inflammation. 2018 Dec;41(6):2196-2205. doi: 10.1007/s10753-018-0862-z.
To investigate the effects of aquaporin 4 (AQP4) inhibitor in irradiation-induced pulmonary inflammation in mice. A single dose of 75 Gy was delivered to the left lung of mice to induce radiation pneumonitis. For inhibition of AQP4, 200 mg/kg of TGN-020 was administered i.p. one time per 2 days post-irradiation. Blockade of AQP4 with TGN-020 resulted in the inhibition of inflammatory cell infiltration and the downregulation of inflammatory cytokines (IL-6, IL-17, and TGF-β), chemokines (MIP1a and MCP1), fibrosis-related (Col3al and Fn1), and M2 macrophage marker (Arg1) post-irradiation. Immunofluorescence staining indicated that there was significant fewer M2 macrophage infiltration in the irradiated lung tissues from mice treated with TGN-020. Additionally, depletion of macrophages with liposome clodronate resulted in alleviated lung injury induced by irradiation. Furthermore, adoptive transfer of M1 or M2 macrophages into clodronate-treated mice was performed. The results showed that the administration of M2 macrophages fully reversed the clodronate-induced beneficial effect on inflammation score, thickness, and fibrosis. However, transfer of M1 macrophages only impacted the inflammation score and thickness and did not affect lung fibrosis. AQP4 blockade alleviated the development and severity of irradiated lung damage. This was associated with attenuated infiltration of inflammatory cell, decreased production of pro-inflammatory cytokines, and inhibited activation of M2 macrophages.
为了研究水通道蛋白 4（AQP4）抑制剂对小鼠照射性肺炎症的影响。将 75Gy 的单次剂量给予小鼠左肺以诱导放射性肺炎。为了抑制 AQP4，在照射后每 2 天腹膜内给予 200mg/kg 的 TGN-020。用 TGN-020 阻断 AQP4 导致炎症细胞浸润减少和炎症细胞因子（IL-6、IL-17 和 TGF-β）、趋化因子（MIP1a 和 MCP1）、纤维化相关（Col3al 和 Fn1）和 M2 巨噬细胞标记物（Arg1）的下调。免疫荧光染色表明，用 TGN-020 处理的照射后小鼠肺组织中 M2 巨噬细胞浸润明显减少。此外，用脂质体氯膦酸盐耗竭巨噬细胞导致照射引起的肺损伤减轻。此外，将 M1 或 M2 巨噬细胞过继转移到氯膦酸盐处理的小鼠中。结果表明，给予 M2 巨噬细胞可完全逆转氯膦酸盐对炎症评分、厚度和纤维化的有益作用。然而，转移 M1 巨噬细胞仅影响炎症评分和厚度，不影响肺纤维化。AQP4 阻断减轻了照射性肺损伤的发展和严重程度。这与炎症细胞浸润减少、促炎细胞因子产生减少以及 M2 巨噬细胞激活抑制有关。
