2. Academic Validation
  3. MiR-223-3p attenuates radiation-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

MiR-223-3p attenuates radiation-induced inflammatory response and inhibits the activation of NLRP3 inflammasome in macrophages

  • Int Immunopharmacol. 2023 Jul 15;122:110616. doi: 10.1016/j.intimp.2023.110616.
Mingwei Zhang 1,  Hailin Lan 2,  Shaoli Peng 3,  Weitong Zhou 3,  Xuezhen Wang 3,  Meina Jiang 3,  Jinsheng Hong 4,  Qiuyu Zhang 5
Affiliations

Affiliations

  • 1 Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China; Department of Radiotherapy, Cancer Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 2 Department of Radiotherapy, Cancer Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 3 Department of Radiotherapy, Cancer Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
  • 4 Department of Radiotherapy, Cancer Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Department of Radiotherapy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, China; Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address: [email protected].
  • 5 Institute of Immunotherapy, Fujian Medical University, Fuzhou, China. Electronic address: [email protected].
PMID: 37459784 DOI: 10.1016/j.intimp.2023.110616
Abstract

Macrophage Pyroptosis plays an important role in the development of radiation-induced cell and tissue damage, leading to acute lung injury. However, the underlying mechanisms of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)-mediated macrophage Pyroptosis and the regulatory factors involved in radiation-induced Pyroptosis are unclear. In this study, the expression of the NLRP3 inflammasome and pyroptosis-associated factors in murine macrophage cell lines was investigated after ionizing radiation. High-throughput RNA sequencing was performed to identify and characterize miRNAs and mRNA transcripts associated with NLRP3-mediated cell death. Our results demonstrated that cleaved-caspase-1 (p10) and N-terminal domain of gasdermin-D (GSDMD-N) were upregulated, and the number of NLRP3 inflammasomes and pyroptotic cells increased in murine macrophage cell lines after irradiation (8 Gy). Comparativeprofiling of 300miRNAs revealed that 41 miRNAsexhibited significantly different expression after 8 Gy of irradiation. Granulocyte-specific microRNA-223-3p (miR-223-3p) is a negative regulator of NLRP3. In vitro experiments revealed that the expression of miR-223-3p was significantly altered by irradiation. Moreover, miR-223-3p decreased the expression of NLRP3 and proinflammatory factors, resulting in reduced Pyroptosis in irradiated murine macrophages. Subsequently, in vivo experiments revealed the efficacy of miR-223-3p supplementation in ameliorating alveolar macrophage (AM) Pyroptosis, attenuating the infiltration of inflammatory monocytes, and significantly alleviating the severity of acute radiation-induced lung injury (ARILI). Our findings suggest that the miR-223-3p/NLRP3/Caspase-1 axis is involved in radiation-induced AM Pyroptosis and ARILI.

Keywords

Macrophage; NLRP3 inflammasome; Pyroptosis; Radiation; miR-223-3p.

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