Frontiers in Pharmacology (Jan 2022)

Autophagy Induced by Micheliolide Alleviates Acute Irradiation-Induced Intestinal Injury via Inhibition of the NLRP3 Inflammasome

  • Dong-ming Wu,
  • Dong-ming Wu,
  • Dong-ming Wu,
  • Jing Li,
  • Jing Li,
  • Rong Shen,
  • Jin Li,
  • Jin Li,
  • Ye Yu,
  • Ye Yu,
  • Li Li,
  • Li Li,
  • Shi-hua Deng,
  • Shi-hua Deng,
  • Teng Liu,
  • Teng Liu,
  • Ting Zhang,
  • Ting Zhang,
  • Ying Xu,
  • Ying Xu,
  • De-gui Wang

DOI
https://doi.org/10.3389/fphar.2021.773150
Journal volume & issue
Vol. 12

Abstract

Read online

Radiation-induced enteropathy (RIE) is one of the most common and fatal complications of abdominal radiotherapy, with no effective interventions available. Pyroptosis, a form of proinflammatory regulated cell death, was recently found to play a vital role in radiation-induced inflammation and may represent a novel therapeutic target for RIE. To investigate this, we found that micheliolide (MCL) exerted anti-radiation effects in vitro. Therefore, we investigated both the therapeutic effects of MCL in RIE and the possible mechanisms by which it may be therapeutic. We developed a mouse model of RIE by exposing C57BL/6J mice to abdominal irradiation. MCL treatment significantly ameliorated radiation-induced intestinal tissue damage, inflammatory cell infiltration, and proinflammatory cytokine release. In agreement with these observations, the beneficial effects of MCL treatment in RIE were abolished in Becn1+/− mice. Furthermore, super-resolution microscopy revealed a close association between NLR pyrin domain three and lysosome-associated membrane protein/light chain 3-positive vesicles following MCL treatment, suggesting that MCL facilitates phagocytosis of the NLR pyrin domain three inflammasome. In summary, MCL-mediated induction of autophagy can ameliorate RIE by NLR pyrin domain three inflammasome degradation and identify MCL as a novel therapy for RIE.

Keywords