Wang Li, Li Zhipeng, He Huan, Qin Lijing, Xu Weiqiang, Tian Hongyuan, Liu Rongrong, Lian Xinru, Li Wen, Qi Yali, Wang Zhicheng
NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin 130021, PR China.
Department of Radiation Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; Medical School of Chinese PLA, Beijing, China.
Ecotoxicol Environ Saf. 2025 Jan 1;289:117625. doi: 10.1016/j.ecoenv.2024.117625. Epub 2025 Jan 2.
Exposure of PM2.5 can cause different degrees of lung injury, which is referred with inflammatory response. Some evidences showed that low-dose radiation (LDR) induces hormesis in immune, however, it is unknown if LDR ameliorates the PM2.5-induced lung injury. Additionally, gut microbiota and inflammation are crucial in lung injury and the health benefits of LDR through gut microbiota need further exploration. Here, we aim to investigate the impact of LDR on PM2.5-induced lung injury in vivo and in vitro, and elucidated the potential mechanisms of anti-inflammation activated by gut microbiota. We observed that LDR ameliorated the lung damage induced by PM2.5 in mice. Additionally, after PM2.5 exposure, M1 polarization of macrophages in alveolar lavage fluid and Th1 polarization in spleen increased, pro-inflammatory cytokines (IL-1, IL-6 and TNF-α) increased and anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) decreased in lung and serum. LDR could deteriorate the changes described as above. Intriguingly, Akkermansia muciniphila (Akk) differed most significantly in the gut microbiota of mice. Notably, PM2.5 activated the Toll-like receptors-induced MyD88/NF-κB pathways to mediate the pro-inflammation, and LDR could inhibited the pathway. However, the TLR1 and TLR2 continuously increased after LDR, indicating the downstream non-canonical TLR1/TLR2 pathway of Akk was activated to blunt the pro-inflammation of PM2.5. Our results strongly indicate that LDR-induced activation of gut Akk-dependent non-canonical TLR1/TLR2-like receptor pathway ameliorates lung injury and inflammation resulted from PM2.5.
暴露于细颗粒物（PM2.5）可导致不同程度的肺损伤，并伴有炎症反应。一些证据表明，低剂量辐射（LDR）可诱导免疫方面的兴奋效应，然而，低剂量辐射是否能改善PM2.5诱导的肺损伤尚不清楚。此外，肠道微生物群和炎症在肺损伤中起关键作用，低剂量辐射通过肠道微生物群产生的健康益处有待进一步探索。在此，我们旨在研究低剂量辐射对体内和体外PM2.5诱导的肺损伤的影响，并阐明肠道微生物群激活的抗炎潜在机制。我们观察到低剂量辐射改善了小鼠中PM2.5诱导的肺损伤。此外，暴露于PM2.5后，肺泡灌洗液中巨噬细胞的M1极化和脾脏中的Th1极化增加，肺和血清中促炎细胞因子（IL-1、IL-6和TNF-α）增加，抗炎细胞因子（IL-4、IL-10和TGF-β）减少。低剂量辐射会加剧上述变化。有趣的是，在小鼠的肠道微生物群中，嗜黏蛋白阿克曼氏菌（Akk）差异最为显著。值得注意的是，PM2.5激活Toll样受体诱导的MyD88/NF-κB途径来介导促炎反应，而低剂量辐射可抑制该途径。然而，低剂量辐射后TLR1和TLR2持续增加，表明Akk的下游非经典TLR1/TLR2途径被激活，以减弱PM2.5的促炎作用。我们的结果有力地表明，低剂量辐射诱导的肠道Akk依赖性非经典TLR1/TLR2样受体途径的激活可改善PM2.5导致的肺损伤和炎症。
