Radiation Biotechnology Division, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup, Republic of Korea.
Department of Biological Sciences and Research Center of Ecomimetics, College of Natural Science, Chonnam National University, Gwangju, Republic of Korea.
PLoS One. 2024 Jun 12;19(6):e0303434. doi: 10.1371/journal.pone.0303434. eCollection 2024.
The modulation of macrophage polarization is a promising strategy for maintaining homeostasis and improving innate and adaptive immunity. Low-dose ionizing radiation has been implicated in macrophage immunomodulatory responses. However, studies on the relationship between exosomes and regulation of macrophage polarization induced by ionizing radiation are limited. Therefore, this study investigated the alterations in macrophages and exosomes induced by gamma irradiation and elucidated the underlying mechanisms. We used the mouse macrophage cell line RAW 264.7 to generate macrophages and performed western blot, quantitative reverse transcription-PCR, and gene ontology analyses to elucidate the molecular profiles of macrophage-derived exosomes under varying treatment conditions, including 10 Gy gamma irradiation. Exosomes isolated from gamma-irradiated M1 macrophages exhibited an enhanced M1 phenotype. Irradiation induced the activation of NF-κB and NLRP3 signaling in M1 macrophages, thereby promoting the expression of pro-inflammatory cytokines. Cytokine expression was also upregulated in gamma-irradiated M1 macrophage-released exosomes. Therefore, gamma irradiation has a remarkable effect on the immunomodulatory mechanisms and cytokine profiles of gamma-irradiated M1 macrophage-derived exosomes, and represents a potential immunotherapeutic modality.
巨噬细胞极化的调节是维持内稳态和改善固有和适应性免疫的一种有前途的策略。低剂量电离辐射与巨噬细胞免疫调节反应有关。然而，关于电离辐射诱导的巨噬细胞极化的外泌体调节的研究有限。因此，本研究探讨了γ 射线照射诱导的巨噬细胞和外泌体的变化，并阐明了潜在的机制。我们使用小鼠巨噬细胞系 RAW 264.7 生成巨噬细胞，并进行 Western blot、定量逆转录-PCR 和基因本体分析，以阐明不同处理条件下（包括 10 Gy γ 射线照射）巨噬细胞来源的外泌体的分子谱。从γ 射线照射的 M1 巨噬细胞中分离出的外泌体表现出增强的 M1 表型。照射诱导 M1 巨噬细胞中 NF-κB 和 NLRP3 信号的激活，从而促进促炎细胞因子的表达。γ 射线照射的 M1 巨噬细胞释放的外泌体中的细胞因子表达也上调。因此，γ 射线照射对 γ 射线照射的 M1 巨噬细胞来源的外泌体的免疫调节机制和细胞因子谱有显著影响，代表了一种潜在的免疫治疗方式。
