Type I <scp>NKT</scp>‐cell‐mediated <scp>TNF</scp>‐α is a positive regulator of <scp>NLRP</scp>3 inflammasome priming

Chow, Melvyn T.; Duret, Helene; Andrews, Daniel M.; Faveeuw, Christelle; Möller, Andreas; Smyth, Mark J.; Paget, Christophe

doi:10.1002/eji.201344329

Cited by 20 publications

(13 citation statements)

References 42 publications

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“…The inflammatory response caused by the NLRP3 inflammasome is triggered in a variety of situations that pose a threat to the host, including TNF-α, the NF-κB pathway, and ROS [9,14,50,51]. In our previous work, we demonstrated that hydrogen treatment activates TNF-α and the NF-κB Fig.…”

Section: Discussionmentioning

confidence: 94%

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

et al. 2020

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Background: Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. Methods: We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1β ELISA were used to analysis pyroptosis between hydrogensupplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. Results: We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosisrelated proteins, and increased the number of PI-and TUNEL-positive cells, as well as the release of LDH and IL-1β, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. Conclusions: This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of antitumor effects in the clinical management of endometrial cancer.

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Section: Discussionmentioning

confidence: 94%

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

et al. 2020

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“…The production of TNF-α is also essential in controlling N. caninum infection [31, 33, 34]. In addition, similar to LPS, TNF-α is sufficient for NLRP3 inflammasome priming [35, 36]. …”

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation in murine macrophages caused by Neospora caninum infection

et al. 2017

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Background Neospora caninum is an intracellular parasite that causes significant economic losses in cattle industry. Understanding the host resistance mechanisms in the innate immune response to neosporosis could facilitate the exploration of approaches for controlling N. caninum infection. The NLR inflammasome is a multiprotein platform in the cell cytoplasm and plays critical roles in the host response against microbes.Methods Neospora caninum-infected wild-type (WT) macrophages and Nlrp3 −/− macrophages, and inhibitory approaches were used to investigate inflammasome activation and its role in N. caninum infection. Inflammasome RT Profiler PCR Arrays were used to identify the primary genes involved in N. caninum infection. The expression of the sensor protein NLRP3, processing of caspase-1, secretion of IL-1β and cell death were detected. Neospora caninum replication in macrophages was also assessed.ResultsMany NLR molecules participated in the recognition of N. caninum, especially the sensor protein NLRP3, and further study revealed that the NLRP3 distribution became punctate in the cell cytoplasm, which facilitated inflammasome activation. Inflammasome activation-mediated caspase-1 processing and IL-1β cleavage in response to N. caninum infection were observed and were correlated with the time of infection and number of infecting parasites. LDH-related cell death was also observed, and this death was regarded as beneficial for the clearance of N. caninum. Treatment of N. caninum-infected macrophages with caspase-1, pan-caspase and NLRP3 inhibitors led to the impaired release of active IL-1β and a failure to restrict parasite replication. And Neospora caninum infected peritoneal macrophages from Nlrp3-deficient mice displayed greatly decreased release of active IL-1β and the failure of caspase-1 cleavage.ConclusionsThe NLRP3 inflammasome can be activated in N. caninum-infected macrophages, and plays a protective role in the host response to control N. caninum.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2197-2) contains supplementary material, which is available to authorized users.

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“…33,34 We and others have demonstrated that TNF-a is sufficient to upregulate proIL-1b protein levels in myeloid cells in vitro and in vivo. 24,25 TNF-a is produced soon after pneumococcal challenge and is predominantly detected in the airways (Figure 4a and Supplementary Figure 4a). In line with the sole presence of AMs in the airways at 6 h postinfection ( Supplementary Figure 4b), intracellular staining revealed that AMs (but not other myeloid cells) were able to produce TNF-a ( Figure 4b).…”

Section: Neutrophil Priming Requires Am-produced Tnf-amentioning

confidence: 99%

“…Recently, we and others have shown that tumor necrosis factor-a (TNF-a) can be instrumental in the transcriptional priming of NLRP3 inflammasome activity in vivo and in vitro by upregulating protein levels of proIL-1b in various myeloid cell populations (including neutrophils). 24,25 tumor necrosis factor-a is an early, ubiquitous cytokine that is massively produced during infections and exerts important biological functions by regulating a wide range of genes in target cells. By binding to two structurally distinct receptors (namely TNF-R1 (CD120a) and TNF-R2 (CD120b)), 26 TNF-a contributes to pleiotropic activities during inflammation such as cell survival/death and the induction of the production of other cytokines.…”

Section: Introductionmentioning

confidence: 99%

Neutrophilic NLRP3 inflammasome-dependent IL-1β secretion regulates the γδT17 cell response in respiratory bacterial infections

et al. 2017

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Traditionally regarded as simple foot soldiers of the innate immune response limited to the eradication of pathogens, neutrophils recently emerged as more complex cells endowed with a set of immunoregulatory functions. Using a model of invasive pneumococcal disease, we highlighted an unexpected key role for neutrophils as accessory cells in innate interleukin (IL)-17A production by lung resident Vγ6Vδ1 T cells via nucleotide-binding oligomerization domain receptor, pyrin-containing 3 (NLRP3) inflammasome-dependent IL-1β secretion. In vivo activation of the NLRP3 inflammasome in neutrophils required both host-derived and bacterial-derived signals. Elaborately, it relies on (i) alveolar macrophage-secreted TNF-α for priming and (ii) subsequent exposure to bacterial pneumolysin for activation. Interestingly, this mechanism can be translated to human neutrophils. Our work revealed the cellular and molecular dynamic events leading to γδT17 cell activation, and highlighted for the first time the existence of a fully functional NLRP3 inflammasome in lung neutrophils. This immune axis thus regulates the development of a protective host response to respiratory bacterial infections.

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Type I NKT‐cell‐mediated TNF‐α is a positive regulator of NLRP3 inflammasome priming

Cited by 20 publications

References 42 publications

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway

NLRP3 inflammasome activation in murine macrophages caused by Neospora caninum infection

Neutrophilic NLRP3 inflammasome-dependent IL-1β secretion regulates the γδT17 cell response in respiratory bacterial infections

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