Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1<i>β</i> and IL-18 in the Septic Response

Luo, Zhuo; Chen, Xiaobing; Sun, Yan; Wang, Yanli; Shi, Yuanfeng; Bu, Lin; Xia, Wei; Han, Jiayan; Chen, Dongmei; Li, Xiaomin

doi:10.1155/2020/5960375

Cited by 27 publications

(18 citation statements)

References 28 publications

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“…A recent study reported that rapamycin, an autophagy agonist, reversed GSDMD-mediated pyroptosis after LPS stimulation. The authors also found that rapamycin alone did not exert an inhibitory effect on pyroptosis and emphasized the important role of autophagy in the entire process [ 56 ].…”

Section: Autophagy Is a Negative Modulator Of Pyroptosismentioning

confidence: 99%

Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis

Guo

Wang

Cui

2021

Mediators of Inflammation

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Sepsis is defined as a life-threatening disease involving multiple organ dysfunction caused by dysregulated host responses to infection. To date, sepsis remains a dominant cause of death among critically ill patients. Pyroptosis is a unique form of programmed cell death mediated by the gasdermin family of proteins and causes lytic cell death and release of proinflammatory cytokines. Although there might be some positive aspects to pyroptosis, it is regarded as harmful during sepsis and needs to be restricted. Autophagy was originally characterized as a homeostasis-maintaining mechanism in living cells. In the past decade, its function in negatively modulating pyroptosis and inflammation during sepsis has attracted increased attention. Here, we present a comprehensive review of the regulatory effect of autophagy on pyroptosis during sepsis, including the latest advances in our understanding of the mechanism and signaling pathways involved, as well as the potential therapeutic application in sepsis.

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Section: Autophagy Is a Negative Modulator Of Pyroptosismentioning

confidence: 99%

Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis

Guo

Wang

Cui

2021

Mediators of Inflammation

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“… 65 The activation of caspase-1 not only promotes pyroptosis, but also promotes the secretion of cytokines such as IL-1β and IL-18, aggravating the inflammatory storm. 74 Our flow cytometry and Western blot analyses showed that EA significantly reduced the apoptosis and pyroptosis of T lymphocytes in endotoxemic mice. EA may prevent the apoptosis and pyroptosis of T lymphocytes and immunosuppression by inhibiting the production of early inflammatory cytokines and apoptosis/pyroptosis-related proteins and signal pathways.…”

Section: Discussionmentioning

confidence: 73%

Electroacupuncture at ST36 (Zusanli) Prevents T-Cell Lymphopenia and Improves Survival in Septic Mice

Lv¹,

Shi²,

Bassi³

et al. 2022

JIR

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Purpose Sepsis is the main cause of death in intensive care unit. Maladaptive cytokine storm and T-cell lymphopenia are critical prognosis predictors of sepsis. Electroacupuncture (EA) is expected to be an effective intervention to prevent sepsis. This study aims to determine the potential of EA at ST36 ( Zusanli ) to prevent experimental septic mice. Methods Mice were randomly assigned into PBS, LPS, or EA+LPS group. EA (0.1 mA, continuous wave, 10 Hz) was performed stimulating the ST36 for 30 min, once a day for 3 days. After the third day, all mice were challenged with PBS or LPS (4 mg/kg) simultaneously. Mice were evaluated for survival, ear temperature, and other clinical symptoms. Lung and small intestine tissue injuries were analyzed by hematoxylin and eosin staining. Bio-Plex cytokine assay was used to analyze the concentration of cytokines. T lymphocytes were analyzed by flow cytometry and Western blot assays. The role of T cells in preventing sepsis by EA was analyzed by using nude mice lacking T lymphocytes. Results EA at ST36 improved survival, symptom scores, and ear temperature of endotoxemic mice. EA also improved dramatically pulmonary and intestinal injury by over 50% as compared to untreated mice. EA blunted the inflammatory cytokine storm by inducing a lasting inhibition of the production of major inflammatory factors (TNF-α, IL-1β, IL-5, IL-6, IL-10, IL-17A, eotaxin, IFN-γ, MIP-1β and KC). Flow cytometry and Western blot analyses showed EA significantly reduced T-lymphocyte apoptosis and pyroptosis. Furthermore, T lymphocytes were critical for the effects of EA at ST36 stimulation blunted serum TNF-α levels in wild-type but not in nude mice. Conclusion EA halted systemic inflammation and improved survival in endotoxemic mice. These effects are associated with the protective effect of EA on T lymphocytes, and T cells are required in the anti-inflammatory effects of EA in sepsis.

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“…EV71 infection induces IL-4, IL-6, IL-12, TNF and IFN production and pyroptosis (36,41). Cells undergoing pyroptosis have been shown to produce IL-1β and IL-18 cytokines, which induce inflammation in the body (42). The present study revealed that EV71 infection induced an increase in the protein level of NLRP3, while it decreased the protein expression levels of GSDMD, pro-caspase-1 and pro-IL-1β in GES-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Total astragalosides decrease apoptosis and pyroptosis by inhibiting enterovirus 71 replication in gastric epithelial cells

et al. 2022

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Enterovirus 71 (EV71) is one of the primary pathogens involved in severe hand, foot and mouth disease in children. EV71 infection causes various types of programmed cell death. However, there are currently no clinically approved specific antiviral drugs for control of EV71 infection. Astragalus membranaceus (AM), a Traditional Chinese medicine, has been used in antiviral therapy in China. The aim of the present study was to determine whether total astragalosides (ASTs), bioactive components of AM, protect against EV. DAPI nuclear staining was used to observe morphological changes of the nucleus and the protective effect of ASTs, which revealed that the nucleus shrank following EV71 infection, while ASTs reversed it. Cell Counting Kit-8 assay found that human normal gastric epithelial cell (GES-1 cell) viability decreased following EV71 infection, while lactate dehydrogenase (LDH) assay showed that EV71 infection induced GES-1 cell damage. Western blotting was used to measure the expression levels of apoptosis and pyroptosis marker protein to determine whether EV71 infection induced apoptosis and pyroptosis in GES-1 cells. Reverse transcription-quantitative PCR was used to determine the anti-EV71 effect of ASTs. The results showed that ASTs protected GES-1 cells from EV71-induced cell apoptosis and pyroptosis. Furthermore, the present data demonstrated that the protective effect of ASTs was exerted by suppressing EV71 replication and release. These findings suggested that ASTs may represent a potential antiviral agent for the treatment of EV71 infection.

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Rapamycin Inhibited Pyroptosis and Reduced the Release of IL-1β and IL-18 in the Septic Response

Cited by 27 publications

References 28 publications

Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis

Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis

Electroacupuncture at ST36 (Zusanli) Prevents T-Cell Lymphopenia and Improves Survival in Septic Mice

Total astragalosides decrease apoptosis and pyroptosis by inhibiting enterovirus 71 replication in gastric epithelial cells

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