Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., Seoul 132-703, Korea.
J Biol Chem. 2012 Aug 10;287(33):27789-95. doi: 10.1074/jbc.M112.378497. Epub 2012 Jun 14.
Mast cells play important roles in many biological responses, such as those during allergic diseases and inflammatory disorders. Although laser and UV irradiation have immunosuppressive effects on inflammatory diseases by suppressing mast cells, little is known about the effects of γ-ionizing radiation on mast cells. In this study, we investigated the effects of γ-ionizing radiation on RBL-2H3 cells, a convenient model system for studying regulated secretion by mast cells. Low-dose radiation (<0.1 gray (Gy)) did not induce cell death, but high-dose radiation (>0.5 Gy) induced apoptosis. Low-dose ionizing radiation significantly suppressed the release of mediators (histamine, β-hexosaminidase, IL-4, and tumor necrosis factor-α) from immunoglobulin E (IgE)-sensitized RBL-2H3 cells. To determine the mechanism of mediator release inhibition by ionizing radiation, we examined the activation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, PKCs, and MAPK, and intracellular free calcium concentrations (Ca(2+)). The phosphorylation of signaling molecules following stimulation of high-affinity IgE receptor I (FcεRI) was specifically inhibited by low-dose ionizing radiation (0.01 Gy). These results were due to the suppression of FcεRI expression by the low-dose ionizing radiation. Therefore, low-dose ionizing radiation (0.01 Gy) may function as a novel inhibitor of mast cell activation.
肥大细胞在许多生物学反应中发挥重要作用,如过敏疾病和炎症性疾病期间。尽管激光和紫外线照射通过抑制肥大细胞对炎症性疾病具有免疫抑制作用,但对γ-电离辐射对肥大细胞的影响知之甚少。在这项研究中,我们研究了γ-电离辐射对 RBL-2H3 细胞的影响,RBL-2H3 细胞是研究肥大细胞调节分泌的便利模型系统。低剂量辐射(<0.1 戈瑞(Gy))不会诱导细胞死亡,但高剂量辐射(>0.5 Gy)会诱导细胞凋亡。低剂量电离辐射显著抑制免疫球蛋白 E(IgE)致敏的 RBL-2H3 细胞释放介质(组胺、β-己糖胺酶、IL-4 和肿瘤坏死因子-α)。为了确定电离辐射抑制介质释放的机制,我们检查了细胞内信号分子(如 Lyn、Syk、磷脂酶 Cγ、PKC 和 MAPK)和细胞内游离钙浓度([Ca(2+)](i))的激活。高亲和力 IgE 受体 I(FcεRI)刺激后信号分子的磷酸化被低剂量电离辐射(0.01 Gy)特异性抑制。这些结果归因于低剂量电离辐射对 FcεRI 表达的抑制。因此,低剂量电离辐射(0.01 Gy)可能作为肥大细胞活化的新型抑制剂发挥作用。