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NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment

Cellular & Molecular Immunology (2024)Cite this article

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Abstract

Inflammasomes are multiprotein complexes involved in the host immune response to pathogen infections. Thus, inflammasomes participate in many conditions, such as acne. Recently, it was shown that NETosis, a type of neutrophil cell death, is induced by bacterial infection and is involved in inflammatory diseases such as delayed wound healing in patients with diabetes. However, the relationship between inflammasomes and NETosis in the pathogenesis of inflammatory diseases has not been well studied. In this study, we determined whether NETosis is induced in P. acnes-induced skin inflammation and whether activation of the nucleotide-binding domain, leucine-rich family, and pyrin domain-containing-3 (NLRP3) inflammasome is one of the key factors involved in NETosis induction in a mouse model of acne skin inflammation. We found that NETosis was induced in P. acnes-induced skin inflammation in mice and that inhibition of NETosis ameliorated P. acnes-induced skin inflammation. In addition, our results demonstrated that inhibiting inflammasome activation could suppress NETosis induction in mouse skin. These results indicate that inflammasomes and NETosis can interact with each other to induce P. acnes-induced skin inflammation and suggest that targeting NETosis could be a potential treatment for inflammasome-mediated diseases as well as NETosis-related diseases.

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Acknowledgements

This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HR21C1003) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (2023R1A2C3002835).

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  1. These authors contributed equally: Hyo Jeong Kim, Yun Sang Lee.

Authors and Affiliations

  1. Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Republic of Korea

    Hyo Jeong Kim, Yun Sang Lee, Bok-Soon Lee, Chang-Hak Han, Sang Gyu Kim & Chul-Ho Kim

  2. Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea

    Chang-Hak Han, Sang Gyu Kim & Chul-Ho Kim

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  1. Hyo Jeong Kim
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Contributions

HJK, B-SL, SGK and C-HH performed the experiments. HJK, YSL and C-HK designed the research and analyzed the results. YSL, HJK and C-HK wrote the manuscript.

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Correspondence to Chul-Ho Kim.

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Kim, H.J., Lee, Y.S., Lee, BS. et al. NLRP3 inflammasome activation and NETosis positively regulate each other and exacerbate proinflammatory responses: implications of NETosis inhibition for acne skin inflammation treatment. Cell Mol Immunol (2024). https://doi.org/10.1038/s41423-024-01137-x

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