Schaue Dörthe, Jahns Jutta, Hildebrandt Guido, Trott Klaus-Rüdiger
Gray Cancer Institute, Northwood, Middlesex, UK.
Int J Radiat Biol. 2005 Sep;81(9):657-67. doi: 10.1080/09553000500385556.
Low-dose radiotherapy (RT) has often been used effectively for the treatment of a variety of benign diseases, particularly those with acute inflammatory features. Here we report findings on radiation treatment of acute inflammation using a murine carrageenin air pouch model.
Air pouches raised on the dorsal surface of mice were injected with lambda carrageenin and were irradiated 6 h later with doses ranging from 0-5 Gy. Treatment success was evaluated at various times thereafter by volume of exudate and number of inflammatory cells, and levels of inflammation-related cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and transforming growth factor beta-1 (TGFbeta-1), and expression of inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and inducible heat shock protein 70 (HSP70) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively.
Crude inflammatory parameters such as the amount of exudates and number of inflammatory cells remained largely unaffected by radiation or were even a slightly and transiently increased. However, the expression of iNOS was attenuated by radiation concomitant with an increase in the levels of HO-1 and HSP70. Cytokine levels varied with the radiation dose and the time point.
Ionizing radiation, even at low doses, functionally modulates inflammatory cells. Our findings indicate possible mechanisms as to how low-dose radiation may exert anti-inflammatory effects and provide the first evidence that heat shock proteins may be involved in this response.
低剂量放疗(RT)常用于有效治疗多种良性疾病,尤其是那些具有急性炎症特征的疾病。在此,我们报告使用小鼠角叉菜胶气囊肿模型进行急性炎症放射治疗的研究结果。
在小鼠背部表面形成气囊肿,向其中注射λ-角叉菜胶,6小时后用0 - 5 Gy的剂量进行照射。此后在不同时间通过渗出液体积、炎症细胞数量、炎症相关细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和转化生长因子β-1(TGFβ-1)水平,以及分别通过酶联免疫吸附测定(ELISA)和蛋白质印迹法测定的诱导型一氧化氮合酶(iNOS)、血红素加氧酶-1(HO-1)、环氧化酶-2(COX-2)和诱导型热休克蛋白70(HSP70)的表达来评估治疗效果。
渗出液量和炎症细胞数量等粗略的炎症参数在很大程度上不受辐射影响,甚至略有短暂增加。然而,辐射使iNOS的表达减弱,同时HO-1和HSP70水平升高。细胞因子水平随辐射剂量和时间点而变化。
电离辐射,即使是低剂量,也能在功能上调节炎症细胞。我们的研究结果表明了低剂量辐射可能发挥抗炎作用的潜在机制,并首次证明热休克蛋白可能参与了这一反应。