NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling

作者：Wu, Tiancong; Gao, Jianhua; Liu, Wen; Cui, Jian; Yang, Miaofang; Guo, Wenjie^*; Wang, Fang-Yu^*

来源：Toxicology and Applied Pharmacology, 2021, 418: 115495.

DOI：10.1016/j.taap.2021.115495

• Radiation
• Tissue Damage
• NLRP3 Inflammasome
• cGAS-STING

In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Furthermore, colon damage, evaluated by H&E staining and barrier function analysis, were significantly aggravated by NLRP3 deficiency. Enhanced phosphorylation of p-TBK1 and p-IRF3 in colonic tissue as well as elevated IFN-13 levels in the serum indicated hyperactivation of cGAS-STING signaling. Moreover, radiation-induced expression of p-TBK1, p-IRF3, and IFN-13 in BMDMs increased in vitro after NLRP3 knockout. Thus, our study outcomes suggest that NLRP3 may protect mice from radiation-induced tissue damage via attenuating cGAS-STING signaling.

• 单位
  南京大学; 南方医科大学; 1