Pin1 Promotes NLRP3 Inflammasome Activation by Phosphorylation of p38 MAPK Pathway in Septic Shock

Dong, Ruijie; Xue, Zhenyi; Fan, Guangyue; Zhang, Na; Wang, Chengzhi; Li, Guangliang; Da, Yurong

doi:10.3389/fimmu.2021.620238

Cited by 21 publications

(13 citation statements)

References 44 publications

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“…It has been reported that the p38 MAPK pathway is closely related to LPS-induced septic shock ( 90 ). A recent study demonstrated that activation of the p38 MAPK pathway promotes NLRP3 inflammasome activation in septic shock ( 91 ). Ang II has been shown to induce NLRP3, in various cardiac cells in a non-septic cardiac damage model, depending on the AT1R/NF-κB or p38 MAPK pathway or crosstalk among them ( 76 , 77 , 92 ).…”

Section: Discussionmentioning

confidence: 99%

Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1–7

Wu¹,

Chen²,

Zhou³

et al. 2023

Ann Transl Med

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Background: Sepsis-induced cardiac dysfunction (SICD) is a common complication of sepsis and contributes to mortality and the complexity of management in patients with sepsis. Recombinant human angiotensin-converting enzyme 2 (rhACE2) has been reported to protect the heart from injury and dysfunction in conditions which involve increased angiotensin II (Ang II). In this study, we aimed to detect the effects of rhACE2 on SICD.Methods: A SICD model was developed in male C57/B6 mice by lipopolysaccharide (LPS) intraperitoneal injection. When cardiac dysfunction was confirmed by echocardiography 3 hours after LPS administration, mice were treated with either saline, rhACE2, or rhACE2 + A779. All mice received echocardiographic examination at 6 hours after LPS injection and then were sacrificed for serum and myocardial tissues collection. Angiotensin, cardiac troponin I (cTnI), and inflammatory markers in serum were measured.Histopathology features were examined by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining to evaluate structure injury and cell pyroptosis rate in heart tissue respectively. Pyroptosis-related proteins and signaling pathways involved in nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in heart tissue were investigated by western blot (WB).Results: RhACE2 relieved myocardial injury and improved cardiac function in mice with SICD accompanied by decrease of Ang II and increase of angiotensin 1-7 (Ang 1-7) in serum. RhACE2 diminished activation of NLRP3 inflammasome, inflammatory response, and cell pyroptosis induced by LPS. In addition, rhACE2 partly inhibited activation of nuclear factor κB (NF-κB), the p38 mitogenactivated protein kinase (MAPK) pathway, and promoted activation of the AMP-activated protein kinase-α1 (AMPK-α1) pathway in heart tissue. Administration of A779 offset the inhibitive effects of rhACE2 on NLRP3 expression and protective role on cardiac injury and dysfunction in mice with SICD.Conclusions: RhACE2 plays a protective role in SICD, ameliorating cardiac injury and dysfunction through NF-κB, p38 MAPK, and the AMPK-α1/NLRP3 inflammasome pathway dependent on converting Ang II to Ang 1-7.

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Section: Discussionmentioning

confidence: 99%

Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1–7

Wu¹,

Chen²,

Zhou³

et al. 2023

Ann Transl Med

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“…Coimmunoprecipitation analysis showed that Pin1 could bind to p-p38, which implied that the p-p38 MAPK might be a substrate of Pin1. Then, with GST pulldown experiment, it showed that Pin1 could not directly bind to p-p38 MAPK in vitro, suggesting that Pin1 might affect p38 MAPK through kinases or other proteins [ 27 ]. In this study, we found that the activation of p38 MAPK was induced by I/R injury and inhibition of Pin1 could suppress p38 MAPK activation in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

The Suppression of Pin1‐Alleviated Oxidative Stress through the p38 MAPK Pathway in Ischemia‐ and Reperfusion‐Induced Acute Kidney Injury

Zhao

Wang

Wan

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Pin1, as the peptidyl-prolyl isomerase, plays a vital role in cellular processes. However, whether it has a regulatory effect on renal ischemia and reperfusion (I/R) injury still remains unknown. Methods. The hypoxia/reoxygenation (H/R) model in human kidney (HK-2) cells and the I/R model in rats were assessed to investigate the role of Pin1 on I/R-induced acute kidney injury. Male Sprague-Dawley rats were used to establish the I/R model for 15, 30, and 45 min ischemia and then 24 h reperfusion, with or without the Pin1 inhibitor, to demonstrate the role of Pin1 in acute kidney injury. HK-2 cells were cultured and experienced the H/R model to identify the molecular mechanisms involved. Results. In this study, we found that Pin1 and oxidative stress were obviously increased after renal I/R. Inhibition of Pin1 with juglone decreased renal structural and functional injuries, as well as oxidative stress. Besides, Pin1 inhibition with the inhibitor, juglone, or the small interfering RNA showed significant reduction on oxidative stress markers caused by the H/R process in vitro. Furthermore, the results indicated that the expression of p38 MAPK was increased during H/R in vitro and Pin1 inhibition could reduce the increased expression of p38 MAPK. Conclusion. Our results illustrated that Pin1 aggravated renal I/R injury via elevating oxidative stress through activation of the p38 MAPK pathway. These findings indicated that Pin1 might become the potential treatment for renal I/R injury.

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“…Under conditions of high ROS levels, TXNIP has been shown to quickly bind inflammasomes and trigger the assembly of inflammasomes (31). Furthermore, phosphorylation of MAPK has been proposed to upregulate transcription of the inflammasome components (32). Therefore, the effects of IL-35 on p38 MAPK and TXNIP expression was examined in bEnd.3 cells subjected to OGD/R.…”

Section: Il-35 Suppressed the Production Of Ros In Ogd/r-induced Bend...mentioning

confidence: 99%

Interleukin-35 attenuates blood-brain barrier dysfunction caused by cerebral ischemia-reperfusion injury through inhibiting brain endothelial cell injury

Qian¹,

Li²,

Lin³

et al. 2022

Ann Transl Med

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Background: , an anti-inflammatory and antioxidant cytokine, plays a potent immunosuppressive role in various diseases. However, the effects of IL-35 on blood-brain barrier (BBB) dysfunction in ischemic stroke are not well characterized.Methods: A total of 150 male C57BL/6 mice (aged 6-8 weeks and weighing 20-25 g) were used in this study. The protective effects of IL-35 against BBB dysfunction were examined using a mouse model of middle cerebral artery occlusion (MCAO) and an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) injury in mouse brain endothelial cells (bEnd.3).Results: Intracerebroventricular administration of IL-35 (10 μg/g) was found to reduce cerebral edema and Evans blue (EB) leakage, and increase the expression of tight junction (TJ) proteins, thereby attenuating MCAO-induced neurological deficit in mice. Moreover, IL-35 (20 ng/mL) treatment upregulated the expression of TJ proteins in OGD/R-induced bEnd.3 cells. IL-35 also markedly suppressed the expression of caspase-1, IL-1β, and gasdermin D (GSDMD) in vivo and in vitro. In addition, IL-35 decreased the generation of reactive oxygen species (ROS) and inhibited the expression of thioredoxin-interacting protein (TXNIP) in OGD/R-induced bEnd.3 cells.Conclusions: These results indicated that IL-35 exerts a protective effect on the BBB by targeting the ROS/TXNIP/caspase-1 pathway in cerebral ischemia-reperfusion (I/R) injury.

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Pin1 Promotes NLRP3 Inflammasome Activation by Phosphorylation of p38 MAPK Pathway in Septic Shock

Cited by 21 publications

References 44 publications

Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1–7

Recombinant human angiotensin-converting enzyme 2 plays a protective role in mice with sepsis-induced cardiac dysfunction through multiple signaling pathways dependent on converting angiotensin II to angiotensin 1–7

The Suppression of Pin1‐Alleviated Oxidative Stress through the p38 MAPK Pathway in Ischemia‐ and Reperfusion‐Induced Acute Kidney Injury

Interleukin-35 attenuates blood-brain barrier dysfunction caused by cerebral ischemia-reperfusion injury through inhibiting brain endothelial cell injury

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