Perforin is recaptured by natural killer cells following target cells stimulation for cytotoxicity

Wang, Lei; Sun, Rulin; Li, Pan; Han, Yang; Xiong, Ping; Xu, Yong; Fang, Min; Tan, Zheng; Zheng, Fang; Gong, Feili

doi:10.1042/cbi20110242

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…Fucoidan (both concentrations) was found to induce cleavage of PARP to the 89 kDa polypeptide (Figure C) after 48 h treatment. From this, it may be assumed that caspases are involved in fucoidan-mediated apoptosis, although caspase-independent PARP cleavage has been reported previously in transforming growth factor β1-induced apoptosis in murine hepatocytes . Induction of PARP cleavage by fucoidans from various sources has been previously reported. ,,, …”

Section: Resultsmentioning

confidence: 89%

“…From this, it may be assumed that caspases are involved in fucoidan-mediated apoptosis, although caspase-independent PARP cleavage has been reported previously in transforming growth factor β1-induced apoptosis in murine hepatocytes. 56 Induction of PARP cleavage by fucoidans from various sources has been previously reported. 22,46,47,51 Apoptotic events are orchestrated primarily, but not exclusively, by members of a family of cysteine aspartate-specific proteases known as caspases.…”

Section: Articlementioning

confidence: 93%

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An Unfractionated Fucoidan from Ascophyllum nodosum: Extraction, Characterization, and Apoptotic Effects in Vitro

et al. 2011

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An unfractionated fucoidan was extracted from the brown alga Ascophyllum nodosum. Extraction of fucoidan from seaweed was carried out using an innovative low-chemical process. A combinational approach involving compositional analysis, HPAEC, IR analysis, GPC, and NMR was employed to elucidate the composition and structure of an unfractionated fucoidan from A. nodosum. This fucoidan is composed mainly of fucose (52.1%), and also galactose (6.1%), glucose (21.3%), and xylose (16.5%). Sulfate content was determined to be 19%. GPC data indicated a polydisperse fucoidan containing two main size fractions (47 and 420 kDa). NMR analyses revealed a fucoidan displaying broad, complex signals as expected for such a high molecular weight and heterogeneous polymer with resonances consistent with a fucoidan isolated previously from A. nodosum. The effects of fucoidan on the apoptosis of human colon carcinoma cells and fucoidan-mediated signaling pathways were also investigated. Fucoidan decreased cell viability and induced apoptosis of HCT116 colon carcinoma cells. Fucoidan treatment of HCT116 cells induced activation of caspases-9 and -3 and the cleavage of PARP, led to apoptotic morphological changes, and altered mitochondrial membrane permeability. These results detail the structure and biological activity of an unfractionated fucoidan from A. nodosum.

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Section: Resultsmentioning

confidence: 89%

Section: Articlementioning

confidence: 93%

An Unfractionated Fucoidan from Ascophyllum nodosum: Extraction, Characterization, and Apoptotic Effects in Vitro

et al. 2011

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“…Perforin is a type of cytotoxic granule found in the cytoplasm of NK cells. When challengers are encountered, NK cells exocytose perforin and granzyme to lyse the target cells [24] , [25] . Thus, the inhibitory effect exerted by DSCs media on perforin production in NK cells could cause NK cells to exhibit a lower level of cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 Secreted by Decidual Stromal Cells Inhibits NK Cells Cytotoxicity by Up-Regulating Expression of SOCS3

Wang

Deng

et al. 2012

PLoS ONE

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BackgroundDecidual stromal cells (DSCs) are of particular importance due to their pleiotropic functions during pregnancy. Although previous research has demonstrated that DSCs participated in the regulation of immune cells during pregnancy, the crosstalk between DSCs and NK cells has not been fully elucidated. To address this issue, we investigated the effect of DSCs on perforin expression in CD56+ NK cells and explored the underlying mechanism.Methodology/Principal FindingsFlow cytometry analysis showed perforin production in NK cells was attenuated by DSC media, and it was further suppressed by media from DSCs pretreated with lipopolysaccharide (LPS). However, the expression of granzyme A and apoptosis of NK cells were not influenced by DSC media. ELISA assays to detect cytokine production indicated that monocyte chemoattractant protein-1 (MCP-1) in the supernatant of DSCs conditioned culture significantly increased after LPS stimulation. The inhibitory effect of DSC media on perforin was abolished by the administration of anti-MCP-1 neutralizing antibody. Notably, reduced perforin expression attenuated the cytotoxic potential of CD56+NK cells to K562 cells. Moreover, Suppressor of cytokine signaling 3 (SOCS3) expression in NK cells was enhanced by treatment with MCP-1, as measured by RT-PCR and western blot. Interestingly, MCP-1-induced perforin expression was partly abolished by the siRNA induced SOCS3 knockdown. Western blot analysis suggested that both NF-κB and ERK/MAPKs pathway were involved in the LPS-induced upregulation of MCP-1 in DSCs.Conclusions/SignificanceOur results demonstrate that LPS induces upregulation of MCP-1 in DSCs, which may play a critical role in inhibiting the cytotoxicity of NK cells partly by promoting SOCS3 expression. These findings suggest that the crosstalk between DSCs and NK cells may be crucial to maintain pregnancy homeostasis.

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“…Perforin has been previously reported to mediate cytotoxicity of human intra-epithelial lymphocytes and serine esterase release [54]. Impaired perforin production causes disrupted NK cell cytotoxicity [55], whereas re-expression of perforin is witnessed as a contributor to the cytotoxic activity of NK cells [56]. This perforin-mediated cytotoxicity is capable of impeding the growth of malignant cells in host tissues and making them dormant for a short duration about at least one month [57].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-20a Mediates the Cytotoxicity of Natural Killer Cells in Endometriosis <i>via</i> ERG/HLX/STAT4/Perforin Axis

Chen¹,

Hu²,

Han³

et al. 2020

SSRN Journal

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Background: Intriguingly, microRNA-20a (miR-20a) has been recently witnessed to be involved in the pathogenesis of endometriosis (EMS) but the molecular mechanism controlled by miR-20a is to be undefined. The present study is designed to probe into how miR-20a acts to regulate the cytotoxicity of natural killer (NK) cells. Methods: Most of all, consistent with the clinical determination in EMS patients, miR-20a was determined to be down-regulated in NK cells isolated from nude mice. miR-20a could specifically bind to ERG and negatively regulates its expression in NK cells. Additionally, shRNA-mediated silencing of ERG decreased the expression of HLX. HLX up-regulated STAT4 by inducing proteasome degradation and inhibited NK cell cytotoxicity. Results: Of great importance, forced expression of miR-20a consequently induced NK cell cytotoxicity in vitro by increasing perforin expression via enhancement of STAT4 that was caused by impairing the binding of ERG to HLX enhancer. The in vivo experiments further confirmed the promoting role of miR-20a in the cytotoxicity of NK cells isolated from EMS nude mice and subsequent protective role of miR-20a against EMS-induced endometrial injury. Conclusion: The aforementioned data suggest that miR-20a potentiates the cytotoxicity of NK via upregulating perforin mediated by ERG/HLX/STAT4, highlighting potential novel mechanisms associated with EMS progression.

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Perforin is recaptured by natural killer cells following target cells stimulation for cytotoxicity

Cited by 6 publications

References 24 publications

An Unfractionated Fucoidan from Ascophyllum nodosum: Extraction, Characterization, and Apoptotic Effects in Vitro

An Unfractionated Fucoidan from Ascophyllum nodosum: Extraction, Characterization, and Apoptotic Effects in Vitro

Monocyte Chemoattractant Protein-1 Secreted by Decidual Stromal Cells Inhibits NK Cells Cytotoxicity by Up-Regulating Expression of SOCS3

MicroRNA-20a Mediates the Cytotoxicity of Natural Killer Cells in Endometriosis <i>via</i> ERG/HLX/STAT4/Perforin Axis

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