Induction of autophagy protects human dental pulp cells from lipopolysaccharide‑induced pyroptotic cell death

Gao, Yang; You, Xinran; Liu, Yubo; Gao, Fei; Zhang, Yuan; Yang, Jianrong; Yang, Chen

doi:10.3892/etm.2020.8475

Cited by 14 publications

(15 citation statements)

References 53 publications

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“…Although autophagy and pyroptosis are two independent patterns of cell death, Jiang et al proved that there is an important feedback network between autophagy, NF-κB signaling pathway and LPS-induced pyroptosis [ 12 ]. Cardiovascular drugs that have been widely used in clinical practice, such as Carvedilol, an α-, β-blocker, are being tested to attenuate macrophage pyroptosis via autophagy activation [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Autophagy blockage promotes the pyroptosis of ox-LDL-treated macrophages by modulating the p62/Nrf2/ARE axis

Liu

Wang

et al. 2021

J Physiol Biochem

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Atherosclerosis, a chronic comprehensive cardiovascular disease, is characterized by the lipid infiltration, formation of foam cells derived from macrophages and inflammation in the vessel wall. Substantial evidence confirms that the activity of autophagic bodies plays a pivot role in regulating cell deaths, but the mechanisms of autophagy to regulate the pyroptosis of macrophages in atherosclerosis remain unclear. In our study, we explored that ox-LDL decreased the cell viability and destroyed the integrity of cell membrane, resulting in the pyroptosis of THP-1 derived macrophages in a dose-dependent manner. Western blotting, qRT-PCR and ELISA also showed that chloroquine (CQ) could up-regulate the expression of p62 through impairing autophagy and induce the pyroptosis of macrophages treated by ox-LDL, as evidenced by the decrease of cell viability and membrane integrity, and the increase of pro-caspase-1, GSDMD, and proinflammatory factors IL-1β and IL-18. Further researches demonstrated that Nrf2, a nuclear factor activated by p62, was linked to macrophage pyroptosis. Overactivating or suppressing Nrf2/ARE signaling would correspondingly aggravate or alleviate pyroptosis, in which the level of p62 was regulated by Nrf2 feedback. Then, bioinformatic analysis verified that there was a close interaction between p62, Nrf2/ARE signaling proteins and pyroptosis-related proteins. Taken together, our results show that blocking autophagy promotes the pyroptosis of ox-LDL-treated macrophages via the p62/Nrf2/ARE axis, providing a novel therapeutic target for atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Autophagy blockage promotes the pyroptosis of ox-LDL-treated macrophages by modulating the p62/Nrf2/ARE axis

Liu

Wang

et al. 2021

J Physiol Biochem

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“…It is demonstrated that RAPA can reduce the pyroptosis in various cell models [ 18 – 20 ] and inhibition of pyroptosis prolong the survival of a sepsis animal model [ 4 , 9 – 11 ]. In the present study, we found that RAPA inhibited pyroptosis and reduced the septic response in both LPS-induced HUVECs and PMA+LPS-activated human THP-1 cell models of sepsis.…”

Section: Discussionmentioning

confidence: 99%

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

Luo

Chen

Sun

et al. 2020

BioMed Research International

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Pyroptosis, an inflammatory form of programmed cell death, is the initiating event of sepsis and results in immune imbalance by releasing IL-1β and IL-18 in the early stages. Studies show that enhancing autophagy via genetic manipulation can inhibit pyroptosis and prolong the survival of a sepsis animal model, indicating a possible therapeutic strategy against sepsis. However, almost no study so far has achieved pyroptosis inhibition via pharmacological autophagy induction in a sepsis disease model. To this end, we established an in vitro sepsis model by stimulating primary human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and analyzed the effect of the autophagy agonist rapamycin (RAPA) on pyroptosis. Phorbol 12-myristate 13-acetate- (PMA-) activated human THP-1 cells were used as the positive control. LPS significantly increased the levels of the pyroptotic protein Gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), secreted LDH, IL-1β, and IL-18. RAPA treatment downregulated the above factors and enhanced autophagy in the LPS-stimulated HUVECs and THP-1 cells. This study shows that RAPA abrogates LPS-mediated increase in IL-1β and IL-18 by inhibiting pyroptosis and enhancing autophagy.

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“…ROS blockade with subsequently suppressed inflammasome activity by autophagy is one of the important mechanisms to antagonize pyroptosis. An important feedback network exists between autophagy, NF-κB signaling pathway, and pyroptosis ( Gao Y. et al, 2020 ). Wang et al reported that enhanced autophagy prevented pyroptotic cell death by eliminating excess ROS and negatively mediating the nuclear translocation of NF-κB P65 and NLRP3 inflammasome activation ( Wang X. et al, 2019 ).…”

Section: Possible Association Between Autophagy and Pyroptosis In Atherosclerosismentioning

confidence: 99%

Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis

Lin

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Atherosclerosis is a chronic inflammatory disorder characterized by the gradual buildup of plaques within the vessel wall of middle-sized and large arteries. The occurrence and development of atherosclerosis and the rupture of plaques are related to the injury of vascular cells, including endothelial cells, smooth muscle cells, and macrophages. Autophagy is a subcellular process that plays an important role in the degradation of proteins and damaged organelles, and the autophagy disorder of vascular cells is closely related to atherosclerosis. Pyroptosis is a proinflammatory form of regulated cell death, while ferroptosis is a form of regulated nonapoptotic cell death involving overwhelming iron-dependent lipid peroxidation. Both of them exhibit distinct features from apoptosis, necrosis, and autophagy in morphology, biochemistry, and genetics. However, a growing body of evidence suggests that pyroptosis and ferroptosis interact with autophagy and participate in the development of cancers, degenerative brain diseases and cardiovascular diseases. This review updated the current understanding of autophagy, pyroptosis, and ferroptosis, finding potential links and their effects on atherogenesis and plaque stability, thus providing ways to develop new pharmacological strategies to address atherosclerosis and stabilize vulnerable, ruptured plaques.

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Induction of autophagy protects human dental pulp cells from lipopolysaccharide‑induced pyroptotic cell death

Cited by 14 publications

References 53 publications

Autophagy blockage promotes the pyroptosis of ox-LDL-treated macrophages by modulating the p62/Nrf2/ARE axis

Autophagy blockage promotes the pyroptosis of ox-LDL-treated macrophages by modulating the p62/Nrf2/ARE axis

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

Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis

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