NXC736 Attenuates Radiation-Induced Lung Fibrosis via Regulating NLRP3/IL-1β Signaling Pathway

Sang Yeon Kim, Sunjoo Park, Ronglan Cui, Hajeong Lee, Hojung Choi, Mohamed El Agamy Farh, Hai In Jo, Jae Hee Lee, Hyo Jeong Song, Yoon Jin Lee, Yun Sil Lee, Bong Yong Lee, Jaeho Cho

Research output: Contribution to journalArticlepeer-review


Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1β and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial–mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.

Original languageEnglish
Article number16265
JournalInternational Journal of Molecular Sciences
Issue number22
StatePublished - Nov 2023

Bibliographical note

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© 2023 by the authors.


  • NLRP3
  • NXC736
  • irradiation
  • radiation-induced lung fibrosis


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