NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1β/IkB-α-NF-κB-NLRP3 feedback loop in swine

Cai, Jingzeng; Guan, Haoyue; Xing, Jinchun; Yang, Jie; Chen, Xiaoming; Zhang, Haoran; Zheng, Yingying; Zhu, Yue; Liu, Qi

doi:10.1016/j.tox.2021.152720

Cited by 72 publications

(15 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several mitochondrial quality-control pathways, including mitophagy, mitochondrial biogenesis, mitochondrial fission and fusion, and antioxidant defenses have been shown to regulate inflammasome activation in various disease states [42][43][44][45]. PGC-1α, which acts as a transcriptional coactivator to promote mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and antioxidant defense, has been shown to regulate inflammasome signaling in different model systems [46][47][48][49][50][51]. For example, in an alcoholic liver-disease model, oroxylin A, a phytochemical, was found to suppress inflammasome ac-tivation through PGC-1α [47].…”

Section: Discussionmentioning

confidence: 99%

The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection

et al. 2022

View full text Add to dashboard Cite

The innate immune response to P. aeruginosa pulmonary infections relies on a network of pattern recognition receptors, including intracellular inflammasome complexes, which can recognize both pathogen- and host-derived signals and subsequently promote downstream inflammatory signaling. Current evidence suggests that the inflammasome does not contribute to bacterial clearance and, in fact, that dysregulated inflammasome activation is harmful in acute and chronic P. aeruginosa lung infection. Given the role of mitochondrial damage signals in recruiting inflammasome signaling, we investigated whether mitochondrial-targeted therapies could attenuate inflammasome signaling in response to P. aeruginosa and decrease pathogenicity of infection. In particular, we investigated the small molecule, ZLN005, which transcriptionally activates peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis, antioxidant defense, and cellular respiration. We demonstrate that P. aeruginosa infection promotes the expression of inflammasome components and attenuates several components of mitochondrial repair pathways in vitro in lung epithelial cells and in vivo in an acute pneumonia model. ZLN005 activates PGC-1α and its downstream effector, Sirtuin 3 (SIRT3), a mitochondrial-localized deacetylase important for cellular metabolic processes and for reactive oxygen species homeostasis. ZLN005 also attenuates inflammasome signaling induced by P. aeruginosa in bronchial epithelial cells and this action is dependent on ZLN005 activation of SIRT3. ZLN005 treatment reduces epithelial-barrier dysfunction caused by P. aeruginosa and decreases pathogenicity in an in vivo pneumonia model. Therapies that activate the PGC-1α—SIRT3 axis may provide a complementary approach in the treatment of P. aeruginosa infection.

show abstract

Section: Discussionmentioning

confidence: 99%

The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection

et al. 2022

View full text Add to dashboard Cite

show abstract

“…All IκB proteins, including IκBα, IκBβ, IκBε, p105/IκBγ and p100/IκBδ, are reported as target genes of NF-κB ( 34 ). Previous studies have demonstrated that IκBα is a transcriptional target for NF-κB, creating a negative feedback loop ( 16 , 35 ). Thus, it was hypothesized that IκBα was not degraded, as NF-κB regulated the synthesis of new IκBα, which entered the nucleus and inhibited the transcriptional function of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

et al. 2021

View full text Add to dashboard Cite

The results of a previous study demonstrated that heat stress (HS) triggered oxidative stress, which in turn induced the apoptosis of epithelial cells. These results uncovered a novel mechanism underlying the activation of NF-κB in primary human umbilical vein endothelial cells. The present study aimed to further investigate the role of NF-κB/IκBα signaling pathways in the inhibition of HS-induced reactive oxygen species (ROS) generation and cytotoxicity in endothelial cells. The results of the present study demonstrated that HS triggered a significant amount of NF-κB and IκBα nuclear translocation without IκBα degradation in a time-dependent manner. Mutant constructs of IκBα phosphorylation sites (Ser32, Ser36) were employed in rat pulmonary microvascular endothelial cells (PMVECs). Cell Counting Kit-8 assays demonstrated that both the small interfering (si)RNA-mediated knockdown of p65 and IκBα mutant constructs significantly decreased cell viability and aggravated ROS accumulation in HS-induced rat PMVECs compared with the control. Additionally, western blot analysis revealed that p65 siRNA attenuated the protein expression of IκBα. However, IκBα mutant constructs failed to attenuate NF-κB activation and nuclear translocation, indicating that IκBα-independent pathways contributed to NF-κB activity and nucleus translocation in a time-dependent manner following HS. Collectively, the results of the present study suggested that the NF-κB/IκBα pathway was essential for resistance to HS-induced ROS production and cytotoxicity in rat PMVECs, and that it could be a potential therapeutic target to reduce the mortality and morbidity of heat stroke.

show abstract

“…The nucleotide-binding domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome complex in BMCs is a critical component that activates innate immune defenses through the mediation of caspase-1 activation and the secretion of proinflammatory IL-1β and IL-18 [ 158 ]. AMPK can inhibit NLRP3 inflammasome complex formation by regulating autophagy [ 159 , 160 ], PGC-1α involvement in mitochondrial function [ 161 ] and endoplasmic reticulum stress [ 162 , 163 ]. Inhibiting AMPK activation induces hyperalgesia associated with NLRP3 inflammasome protein activation and increased serum levels of IL-1β and IL-18.…”

Section: Potential Mechanism Of Non-neuronal Ampk In Pain Regulationmentioning

confidence: 99%

Roles of AMPK and Its Downstream Signals in Pain Regulation

Wang

Dai

2021

Life

View full text Add to dashboard Cite

Pain is an unpleasant sensory and emotional state that decreases quality of life. A metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK), which is ubiquitously expressed in mammalian cells, has recently attracted interest as a new target of pain research. Abnormal AMPK expression and function in the peripheral and central nervous systems are associated with various types of pain. AMPK and its downstream kinases participate in the regulation of neuron excitability, neuroinflammation and axonal and myelin regeneration. Numerous AMPK activators have reduced pain behavior in animal models. The current understanding of pain has been deepened by AMPK research, but certain issues, such as the interactions of AMPK at each step of pain regulation, await further investigation. This review examines the roles of AMPK and its downstream kinases in neurons and non-neuronal cells, as well as their contribution to pain regulation.

show abstract

NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1β/IkB-α-NF-κB-NLRP3 feedback loop in swine

Cited by 72 publications

References 60 publications

The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection

The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection

NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

Roles of AMPK and Its Downstream Signals in Pain Regulation

Contact Info

Product

Resources

About