Original Paper | Published:

Caspase-4 activation by a bacterial surface protein is mediated by cathepsin G in human gingival fibroblasts

Cell Death and Differentiation volume 25, pages 380391 (2018) | Download Citation

Edited by RA Knight

Abstract

Caspase-4 is an inflammatory caspase; however, its mechanism of activation is poorly understood. In this study, we demonstrate that Td92, a surface protein of the periodontal pathogen Treponema denticola and a homolog of the Treponema pallidum surface protein Tp92, activates caspase-4 and induces pyroptosis in primary cultured human gingival fibroblasts (HGFs) via cathepsin G activation. Cathepsin G inhibition or siRNA knockdown of cathepsin G inhibited Td92-induced caspase-4 activation and cell death. Td92-induced cell death was significantly inhibited by siRNA knockdown of gasdermin D. Td92 treatment resulted in the binding of cathepsin G to caspase-4 and the coaggregation of these two molecules. In addition, Td92 induced IL-1α expression and secretion, and this was inhibited by caspase-4 knockdown. Cytochalasin D did not block Td92-induced caspase-4 activation, suggesting that Td92 internalization is not required for caspase-4 activation. Our results demonstrate that cathepsin G is directly engaged in caspase-4 activation by a bacterial ligand, which is responsible for cell death and IL-1α secretion in HGFs.

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Acknowledgements

This study was supported by grants from the Basic Science Research Program of the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (NRF-2015R1A2A2A01002598).

Author information

Author notes

    • Hye-Kyoung Jun

    Current address: Institute of Bone Science, OSSTEM IMPLANT Co., Ltd, Seoul 02861, Republic of Korea

    • Young-Jung Jung

    Current address: Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KT 402, USA

Affiliations

  1. Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea

    • Hye-Kyoung Jun
    • , Young-Jung Jung
    • , Sun-Jin An
    •  & Bong-Kyu Choi
  2. Department of Periodontology, Ajou University Hospital, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea

    • Suk Ji
  3. Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea

    • Bong-Kyu Choi

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Bong-Kyu Choi.

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DOI

https://doi.org/10.1038/cdd.2017.167

Supplementary Information accompanies this paper on Cell Death and Differentiation website (http://www.nature.com/cdd)