Inhibition of AIM2 inflammasome-mediated pyroptosis by Andrographolide contributes to amelioration of radiation-induced lung inflammation and fibrosis

Cell Death Dis. 2019 Dec 20;10(12):957. doi: 10.1038/s41419-019-2195-8.

Abstract

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we report the potential radioprotective effect and mechanism of Andrographolide on RILI. C57BL/6 mice were exposed to 18 Gy of whole thorax irradiation, followed by intraperitoneal injection of Andrographolide every other day for 4 weeks. Andrographolide significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine release in the early phase and progressive fibrosis in the late phase. Moreover, Andrographolide markedly hampered radiation-induced activation of the AIM2 inflammasome and pyroptosis in vivo. Furthermore, bone marrow-derived macrophages (BMDMs) were exposed to 8 Gy of X-ray radiation in vitro and Andrographolide significantly inhibited AIM2 inflammasome mediated-pyroptosis in BMDMs. Mechanistically, Andrographolide effectively prevented AIM2 from translocating into the nucleus to sense DNA damage induced by radiation or chemotherapeutic agents in BMDMs. Taken together, Andrographolide ameliorates RILI by suppressing AIM2 inflammasome mediated-pyroptosis in macrophage, identifying Andrographolide as a novel potential protective agent for RILI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Radiation-Induced / drug therapy*
  • Abnormalities, Radiation-Induced / genetics
  • Abnormalities, Radiation-Induced / pathology
  • Animals
  • DNA-Binding Proteins / genetics*
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Humans
  • Inflammasomes / drug effects
  • Inflammasomes / genetics
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation / pathology
  • Lung / abnormalities
  • Lung / drug effects
  • Lung / radiation effects
  • Lung Injury / drug therapy*
  • Lung Injury / etiology
  • Lung Injury / pathology
  • Mice
  • Pyroptosis / drug effects
  • Pyroptosis / genetics
  • Radiation-Protective Agents / pharmacology

Substances

  • Aim2 protein, mouse
  • DNA-Binding Proteins
  • Diterpenes
  • Inflammasomes
  • Radiation-Protective Agents
  • andrographolide