Skip to main content

Advertisement

SpringerLink
Log in

The Influence of Radiotherapy on AIM2 Inflammasome in Radiation Pneumonitis

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

This study aims to investigate the influence of radiotherapy on absent in melanoma 2 (AIM2) inflammasome in radiation pneumonitis (RP). A rat model of RP was established. H&E staining was used to test radiation-induced lung tissue injury. Immunohistochemistry (IHC) was used to detect the expression of AIM2 and IL-1β in rat lung tissues. Milliplex assay was used to test cytokine levels in rat serum. Comet assay was adopted to examine DNA breaks in THP1 cells. RT-PCR was used to detect the messenger RNA (mRNA) expression of AIM2, caspase-1, and IL-1β in THP1 cells. As a result, the rat model indicated that irradiation induced obvious lung injury. A large amount of inflammatory cells infiltrated to the irradiated lung tissues. The structure of lung tissues collapsed. IHC revealed that AIM2 and IL-1β expressions were significantly higher in irradiated lung tissues than in the control. IL-1β level in rat serum significantly elevated on the 7th day post-irradiation, gradually decreased on the 15th day, and became minimal on the 30th day. Irradiation induced dsDNA break in a dose-dependent manner at 24 h after irradiation. Radiotherapy increased the mRNA expression level of AIM2 and IL-1β in a time-dependent manner. In conclusion, radiotherapy triggered some critical components of AIM2 inflammasome in RP. The activation of AIM2 inflammasome by radiotherapy may contribute to the pathogenesis of RP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Li, J., S. Mu, L. Mu, et al. 2015. Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study. Oncology Targets Therapy 8: 1129–1136.

    Article  CAS  Google Scholar 

  2. Can, Demirel, C.K. Sevil, G. Serkan, et al. 2016. Inhibition of radiation-induced oxidative damage in the lung tissue: may acetylsalicylic acid have a positive role? Inflammation 39: 158–165.

    Article  Google Scholar 

  3. Rodrigues, G., M. Lock, D. D’Souza, et al. 2004. Prediction of radiation pneumonitis by dose -volume histogram parameters in lung cancer-a systematic review. Radiotherapy and Oncology 71: 127–138.

    Article  PubMed  Google Scholar 

  4. Ding, N.H., J.J. Li, and L.Q. Sun. 2013. Molecular mechanisms and treatment of radiation-induced lung fibrosis. Current Drug Targets 14: 1347–1356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sohn, S.H., J.M. Lee, S. Park, et al. 2015. The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice. Environmental Toxicology and Pharmacology 39: 917–926.

    Article  CAS  PubMed  Google Scholar 

  6. Chen, L.C., L.J. Wang, N.M. Tsang, et al. 2012. Tumor inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma. EMBO Molecular Medicine 4: 1276–1293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Latz, Eicke, T.S. Xiao, and Andrea Stutz. 2013. Activation and regulation of the inflammasomes. Nature Reviews Immunology 13: 397–411.

    Article  CAS  PubMed  Google Scholar 

  8. Dombrowski, Y., M. Peric, S. Koglin, et al. 2011. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Science Translational Medicine 3: 82ra38.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Derer, A., L. Deloch, Y. Rubner, et al. 2015. Radio-immunotherapy-induced immunogenic cancer cells as basis for induction of systemic anti-tumor immune responses- pre-clinical evidence and ongoing clinical applications. Frontiers in Immunology 6: 505.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fernandes-Alnemri, T., J.W. Yu, P. Datta, et al. 2009. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458: 509–513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xiang, F., Z. Ni, Y. Zhan, et al. 2016. Increased expression of MyD88 and association with paclitaxel resistance in breast cancer. Tumor Biology 37: 6017–6025.

    Article  CAS  PubMed  Google Scholar 

  12. Henry, C.J., R.L. Sedjo, A. Rozhok, et al. 2015. Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma. BMC Cancer 15: 123.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Zheng, H., S. Wang, P. Zhou, et al. 2013. Effects of ligustrazine on DNA damage and apoptosis induced by irradiation. Environmental Toxicology and Pharmacology 36: 1197–1206.

    Article  CAS  PubMed  Google Scholar 

  14. Zaidi, A., S. Jelveh, J. Mahmood, et al. 2012. Effects of lipopolysaccharide on the response of C57BL/6J mice to whole thorax irradiation. Radiotherapy and Oncology 105: 341–349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Han, Y., Z. Chen, R. Hou, et al. 2015. Expression of AIM2 is correlated with increased inflammation in chronic hepatitis B patients. Virology Journal 12: 129.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Liu, G.D., L. Xia, J.W. Zhu, et al. 2014. Genistein alleviates radiation-induced pneumonitis by depressing Ape1/Ref-1 expression to down-regulate inflammatory cytokines. Cell Biochemistry and Biophysics 69: 725–733.

    Article  CAS  PubMed  Google Scholar 

  17. Yoshino, H., T. Kiminarita, Y. Matsushita, et al. 2012. Response of the Nrf2 protection system in human monocytic cells after ionising irradiation. Radiation Protection Dosimetry 152: 104–108.

    Article  CAS  PubMed  Google Scholar 

  18. Rall, M., D. Kraft, M. Volcic, et al. 2015. Impact of charged particle exposure on homologous DNA double-strand break repair in human blood-derived cells. Frontiers Oncology 5: 250.

    Article  Google Scholar 

  19. Nakahira, K., J.A. Haspel, V.A. Rathinam, et al. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nature Immunology 12: 222–230.

    Article  CAS  PubMed  Google Scholar 

  20. Shimada, K., T.R. Crother, J. Karlin, et al. 2012. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36: 401–414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Santoro, R., M. Ferraiuolo, G.P. Morgano, et al. 2016. Comet assay in cancer chemoprevention. Methods in Molecular Biology 1379: 99–105.

    Article  PubMed  Google Scholar 

  22. Chen, Y., J. Williams, I. Ding, et al. 2002. Radiation pneumonitis and early circulatory cytokine markers. Seminars in Radiation Oncology 12: 26–33.

    Article  PubMed  Google Scholar 

  23. Rajeshwari, H. Patil, R.L. Babu, M. Naveen Kumar, et al. 2016. Anti-inflammatory effect of apigenin on LPS-induced pro-inflammatory mediators and AP-1 factors in human lung epithelial cells. Inflammation 39: 138–147.

    Article  Google Scholar 

  24. Man, S.M., and T.D. Kanneganti. 2015. Regulation of inflammasome activation. Immunology Reviews 265: 6–21.

    Article  CAS  Google Scholar 

  25. Christo, Susan, Akash Bachhuka, Kerrilyn R. Diener, et al. 2016. The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry. Science Reports 6: 26207.

    Article  CAS  Google Scholar 

  26. Johnston, C.J., J.P. Williams, A. Elder, et al. 2004. Inflammatory cell recruitment following thoracic irradiation. Experimental Lung Research 30: 369–382.

    Article  CAS  PubMed  Google Scholar 

  27. Man, S.M., R. Karki, and T.D. Kanneganti. 2016. AIM2 inflammasome in infection, cancer and autoimmunity: role in DNA sensing, inflammation and innate immunity. European Journal of Immunology 46: 269–280.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was sponsored by National Natural Science Foundation of China (NO. 81372407).

Author information

Author notes

    Authors and Affiliations

    1. Department of Oncology I, Renmin Hospital of Wuhan University, 430060, Wuhan, China

      Qianyu Zhang, Qinyong Hu, Yuxin Chu, Bin Xu & Qibin Song

    Authors
    1. Qianyu Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Qinyong Hu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yuxin Chu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Bin Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Qibin Song
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Qibin Song.

    Ethics declarations

    Conflict of Interest

    The authors declare that there is no conflict of interest.

    Additional information

    Qianyu Zhang and Qinyong Hu contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhang, Q., Hu, Q., Chu, Y. et al. The Influence of Radiotherapy on AIM2 Inflammasome in Radiation Pneumonitis. Inflammation 39, 1827–1834 (2016). https://doi.org/10.1007/s10753-016-0419-y

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10753-016-0419-y

    KEY WORDS

    Search

    Navigation