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

Jun, Hye‐Kyoung; Jung, Young‐Jung; Ji, Sang-Hoon; An, Sun‐Jin; Choi, Bong‐Kyu

doi:10.1038/cdd.2017.167

Cited by 26 publications

(29 citation statements)

References 48 publications

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“…However, the pathogenic effect of Tp92 remains poorly understood. In a recent study, Jun et al demonstrated that Td92, a surface protein of the periodontal pathogen Treponema denticola and a homologue of the T. pallidum surface protein Tp92, activates caspase‐4 and induces pyroptosis in primary cultured human gingival fibroblasts via cathepsin G activation . In the present study, we investigated the potential pathogenic role of the outer membrane protein Tp92 by exploring the effect of Tp92 on the THP‐1 innate immune response cells.…”

Section: Introductionmentioning

confidence: 91%

“…In a recent study, Jun et al demonstrated that Td92, a surface protein of the periodontal pathogen Treponema denticola and a homologue of the T. pallidum surface protein Tp92, activates caspase-4 and induces pyroptosis in primary cultured human gingival fibroblasts via cathepsin G activation. 16 In the present study, we investigated the potential pathogenic role of the outer membrane protein Tp92 by exploring the effect of Tp92 on the THP-1 innate immune response cells. Healthy volunteers with no syphilis infection were recruited and were confirmed to be seronegative for syphilis by serological tests conducted by the Second Affiliated Hospital of University of South China.…”

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confidence: 99%

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The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL‐8 secretion

Luo

Zhang

Gan

et al. 2018

J Cellular Molecular Medi

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Treponema pallidum is the pathogen that causes syphilis, a sexually transmitted disease; however, the pathogenic mechanism of this organism remains unclear. Tp92 is the only T. pallidum outer membrane protein that has structural features similar to the outer membrane proteins of other Gram‐negative bacteria, but the exact functions of this protein remain unknown. In the present study, we demonstrated that the recombinant Tp92 protein can induce human mononuclear cell death. Tp92 mediated the human monocytic cell line derived from an acute monicytic leukemia patient (THP‐1) cell death by recognizing CD14 and/or TLR2 on cell surfaces. After the stimulation of THP‐1 cells by the Tp92 protein, Tp92 may induce atypical pyroptosis of THP‐1 cells via the pro‐caspase‐1 pathway. Meanwhile, this protein caused the apoptosis of THP‐1 cells via the receptor‐interacting protein kinase 1/caspase‐8/aspase‐3 pathway. Tp92 reduced the number of monocytes among peripheral blood mononuclear cells. Interestingly, further research showed that Tp92 failed to increase the tumour necrosis factor‐α, interleukin (IL)‐1β, IL‐6, IL‐10, IL‐18 and monocyte chemotactic protein 1 (MCP)‐1 levels but slightly elevated the IL‐8 levels via the Nuclear Factor (NF)‐κB pathway in THP‐1 cells. The data suggest that Tp92 recognizes CD14 and TLR2, transfers the signal to a downstream pathway, and activates NF‐κB to mediate the production of IL‐8. This mechanism may help T. pallidum escape recognition and elimination by the host innate immune system.

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Section: Introductionmentioning

confidence: 91%

mentioning

confidence: 99%

The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL‐8 secretion

Luo

Zhang

Gan

et al. 2018

J Cellular Molecular Medi

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“…IL-1 α secretion is caspase-1 independent [ 19 ] but is positively correlated with the activity of caspase-4 [ 7 , 20 ], a key factor of the noncanonical pathway. The secretion of IL-1 β and IL-18 is positively correlated with the activity of caspase-1, a key factor of the canonical pathway [ 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the canonical pathway was inhibited in NLRP1 knockdown MCF7 cells, and hUCMSC-CM-induced pyroptosis in these cells mainly occurs via the caspase-4-mediated noncanonical pathway. IL-1α secretion is caspase-1 independent [19] but is positively correlated with the activity of caspase-4 [7,20], a key factor of the noncanonical pathway. The secretion of IL-1β and IL-18 is positively correlated with the activity of caspase-1, a key factor of the canonical pathway [21,22].…”

mentioning

confidence: 99%

The Role of Caspase-4 and NLRP1 in MCF7 Cell Pyroptosis Induced by hUCMSC-Secreted Factors

Jiao

Wang

Lü

et al. 2020

Stem Cells International

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Mesenchymal stem cells (MSCs) are being widely investigated for the development of novel therapeutic approaches for different cancers, including breast cancer, the leading form of cancer in women. Our previous study showed that the factors secreted by human umbilical cord MSCs (hUCMSCs) induced pyroptosis in the breast cancer cell line MCF7 and our RNA sequencing studies revealed an increase in the expression of the pyroptosis-related gene caspase-4 (CASP4) and nucleotide-binding, leucine-rich repeat pyrin domain-containing protein 1 (NLRP1) in pyroptotic MCF7 cells. Cellular pyroptosis can occur via the canonical pathway (involving caspase-1 and NLRP1) or the noncanonical pathway (involving caspase-4). In this study, we first confirmed that the inflammasome complex formed by NLRP1 and ASC is involved in MCF7 cell pyroptosis induced by hUCMSC-CM. Further, we investigated the role of CASP4 and NLRP1 in MCF7 cell pyroptosis induced by hUCMSC-secreted factors using shRNA-mediated transfection of CASP4 or NLRP1 in MCF7 cells. Cytotoxicity analyses revealed that neither CASP4 knockdown nor NLRP1 knockdown could inhibit the hUCMSC-CM-induced pyroptosis in MCF7 cells. Gene and protein expression analysis showed that hUCMSC-CM induced pyroptosis mainly via the canonical pathway in CASP4 knockdown MCF7 cells but mainly via the noncanonical pathway in NLRP1 knockdown MCF7 cells. Our study provides a foundation for further studies aimed at elucidating the precise mechanism underlying hUCMSC-induced pyroptosis in breast cancer cells and aid the identification of potential therapeutic targets for breast cancer.

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“…Immunoblotting was performed as previously described with slight modifications (Jun et al, ). After cells were treated with bacteria (see 2.2 cell treatment), culture supernatants were separately collected from the cells.…”

Section: Methodsmentioning

confidence: 99%

Regulation of IL‐24 in human oral keratinocytes stimulated with Tannerella forsythia

Han

et al. 2019

Molecular Oral Microbiology

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Interleukin-24 is a pleiotropic immunoregulatory cytokine and a member of the IL-20R subfamily of the IL-10 family. The aim of this study was to investigate the regulation of IL-24 in the human oral keratinocyte cell line HOK-16B following infection with Tannerella forsythia, a major periodontal pathogen. T. forsythia induced the expression of IL-24 mRNA and the secretion of glycosylated IL-24 in HOK-16B cells.Glycosylation of IL-24 is linked to its solubility and bioavailability. T. forsythia-stimulated reactive oxygen species (ROS) induced the expression of IL-24, which was regulated by IL-6. The ROS inhibitor N-acetylcysteine and MAPK inhibitors significantly reduced the expression of IL-6 and IL-24 induced by T. forsythia. Recombinant human IL-24 significantly enhanced the expression of IL-1α, IL-8, CXCL10, and MCP-1 in HOK-16B cells. Together, these results indicate that ROS, MAPKs, and IL-6 comprise the axis of IL-24 expression in HOK-16B cells stimulated with T. forsythia. Thus, IL-24 may be involved in inflammation in oral keratinocytes. K E Y W O R D S IL-24, oral keratinocytes, periodontal pathogen, reactive oxygen species

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

Cited by 26 publications

References 48 publications

The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL‐8 secretion

The outer membrane protein Tp92 of Treponema pallidum induces human mononuclear cell death and IL‐8 secretion

The Role of Caspase-4 and NLRP1 in MCF7 Cell Pyroptosis Induced by hUCMSC-Secreted Factors

Regulation of IL‐24 in human oral keratinocytes stimulated with Tannerella forsythia

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