Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo

Li, Ziyin; Chi, Huiqin; Zhu, Wei; Yang, Guangyu; Song, Jia; Mo, Lijun; Zhang, Yitian; Deng, Ya; Xu, Feifei; Yang, Jiani; He, Zhini; Yang, Xingfen

doi:10.1007/s00204-021-03157-2

Cited by 60 publications

(21 citation statements)

References 64 publications

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“…27 Cd induced renal inflammation through ROS/MAPK/NF-κB signaling pathway. 60 Our data showed that NAC reduced inflammation induced by co-treatment with PS-NPs and LPS, confirming the ROS/MAPK involved in that PS-NPs promoted LPS-induced inflammation.…”

Section: Discussionsupporting

confidence: 76%

Polystyrene nanoplastics exacerbated lipopolysaccharide‐induced necroptosis and inflammation via the ROS/MAPK pathway in mice spleen

Tang

Fan

et al. 2022

Environmental Toxicology

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Plastics are novel environmental pollutants with potential threats to the ecosystem. At least 5.25 trillion plastic particles in the environment, of which nanoplastics are <100 nm in diameter. Polystyrene nanoplastics (PS‐NPs) exposure damaged the spleen's immune function. Lipopolysaccharide (LPS) induced other toxicants to damage cells and organs, triggering inflammation. However, the mechanism of PS‐NPs aggravated LPS‐induced spleen injury remains unclear. In this study, the PS‐NPs or/and LPS mice exposure model was replicated by intraperitoneal injection of PS‐NPs or/and LPS, and PS‐NPs or/and LPS were exposed to RAW264.7 cells. The histopathological and ultrastructural changes of the mice spleen were observed by H&E staining and transmission electron microscope. Western Blot, qRT‐PCR, and fluorescent probes staining were used to detect reactive oxygen species (ROS), oxidative stress indicators, inflammatory factors, and necroptosis‐related indicators in mice spleen and RAW264.7 cells. The results showed that PS‐NPs or LPS induced oxidative stress, activated the MAPK pathway, and eventually caused necroptosis and inflammation in mice spleen and RAW264.7 cells. Compared with the single treatment group, the changes in PS‐NPs + LPS group were more obvious. Furthermore, ROS inhibitor N‐Acetyl‐L‐cysteine (NAC) significantly inhibited the activation of the mitogen‐activated protein kinase (MAPK) signaling pathway caused by co‐treatment of PS‐NPs and LPS, reducing necroptosis and inflammation. The results demonstrated that PS‐NPs promoted LPS‐induced spleen necroptosis and inflammation in mice through the ROS/MAPK pathway. This study increases the data on the damage of PS‐NPs to the organism and expands the research ideas and clues.

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Section: Discussionsupporting

confidence: 76%

Polystyrene nanoplastics exacerbated lipopolysaccharide‐induced necroptosis and inflammation via the ROS/MAPK pathway in mice spleen

Tang

Fan

et al. 2022

Environmental Toxicology

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“…The potential reason might be that HDAC4 might inhibit inflammation through several pathways, such as mitogen‐activated protein kinase and nuclear factor kappa‐B signaling pathways. 20 , 21 , 22 , 23 Furthermore, ICAM‐1 and VCAM‐1 are involved in the all stage of atherosclerosis, an important risk factor in pathology of AIS. 15 Hence, we detected the level of ICAM‐1 and VCAM‐1 in AIS patients, which showed that negative correlation was found between HDAC4 and these adhesion molecules.…”

Section: Discussionmentioning

confidence: 99%

“…To solve this issue, we detected several inflammatory cytokines in AIS patients and explored their association with HDAC4 in the current study, which presented that HDAC4 was negatively correlated with inflammation to some extent. The potential reason might be that HDAC4 might inhibit inflammation through several pathways, such as mitogen‐activated protein kinase and nuclear factor kappa‐B signaling pathways 20‐23 . Furthermore, ICAM‐1 and VCAM‐1 are involved in the all stage of atherosclerosis, an important risk factor in pathology of AIS 15 .…”

Section: Discussionmentioning

confidence: 99%

Clinical role of serum histone deacetylase 4 measurement in acute ischemic stroke: Relation to disease risk, severity, and prognosis

Wang

Pang

et al. 2022

Clinical Laboratory Analysis

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Objective Histone deacetylase 4 (HDAC4) is engaged in the pathophysiology of acute ischemic stroke (AIS) through modulating atherosclerosis, inflammation and neurocyte death. This study aimed to investigate the clinical role of HDAC4 in AIS. Methods Serum samples were collected from 176 AIS patients and 80 controls for HDAC4 detection by enzyme‐linked immunosorbent assay (ELISA). In AIS patients, disease severity was assessed by National Institute of Health Stroke Scale (NIHSS) score and their recurrence‐free survival (RFS) and overall survival (OS) were calculated, inflammatory cytokines and adhesion molecules were detected by ELISA. Results HDAC4 was declined in AIS patients vs. controls (p < 0.001), it also had certain ability of distinguishing AIS patients from controls with an area under curve of 0.748 (95% confidence interval: 0.689–0.806). Among AIS patients, HDAC4 was negatively linked with NIHSS score (p < 0.001) but no other clinical features (all p > 0.05). Moreover, HDAC4 was negatively related to interleukin (IL)‐17 (p = 0.010) and tumor necrosis factor alpha (p = 0.001), while it was not correlated with IL‐1β (p = 0.081) or IL‐6 (p = 0.074). Furthermore, HDAC4 was negatively associated with intercellular cell adhesion molecule‐1 (p < 0.001) and vascular cell adhesion molecule‐1 (p = 0.003). During a median follow‐up of 19.0 months, 17 (9.7%) patients had recurrence and 10 (5.7%) patients died. Additionally, high HDAC4 was linked with prolonged RFS (p = 0.044) but not OS (p = 0.079). Conclusion HDAC4 possesses the potential to monitor disease risk, inflammation and estimate recurrence of AIS, while further study with larger scale is needed to verify our findings.

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“…Once primed, PAMPs or DAMPs through their ability to bind to either the purinergic P2X7 receptor (P2X7R; DAMPS) ( Yiwen Zhang et al, 2021 ) or toll-like receptors (TLRs; PAMPs), activate the NLRP3 inflammasome through recruitment and binding of ASC and pro-caspase-1 to NLRP3 ( Mangan et al, 2018 ). This predominantly leads to potassium efflux ( Wang and Hauenstein, 2020 ), but can evoke changes in intracellular calcium ( Jäger et al, 2020 ), lysosome destabilisation ( Svadlakova et al, 2020 ) and the production of reactive oxygen species (ROS) ( Li et al, 2021 ).…”

Section: The Nlrp3 Inflammasomementioning

confidence: 99%

The Role of the NLRP3 Inflammasome in Mediating Glomerular and Tubular Injury in Diabetic Nephropathy

et al. 2022

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The NOD-like receptor protein 3 (NLRP3) inflammasome is a multi-protein signalling complex integral to the chronic inflammatory response, activated in response to sterile and non-sterile cellular damage. The assembly and activation of the NLRP3 inflammasome comprise a two-step process involving nuclear factor kappa B (NFkB)-mediated priming, followed by canonical, non-canonical or alternative signalling pathways. These result in the maturation and release of inflammatory cytokines interleukin 1 beta (IL1ß) and interleukin-18 (IL18), which are associated with chronic inflammatory conditions including diabetic kidney disease. Diabetic nephropathy is a condition affecting ∼40% of people with diabetes, the key underlying pathology of which is tubulointerstitial inflammation and fibrosis. There is growing evidence to suggest the involvement of the NLRP3 inflammasome in this chronic inflammation. Early deterioration of kidney function begins in the glomerulus, with tubular inflammation dictating the progression of late-stage disease. Priming and activation of the NLRP3 inflammasome have been linked to several clinical markers of nephropathy including proteinuria and albuminuria, in addition to morphological changes including mesangial expansion. Treatment options for diabetic nephropathy are limited, and research that examines the impact of directly targeting the NLRP3 inflammasome, or associated downstream components are beginning to gain favour, with several agents currently in clinical trials. This review will explore a role for NLRP3 inflammasome activation and signalling in mediating inflammation in diabetic nephropathy, specifically in the glomerulus and proximal tubule, before briefly describing the current position of therapeutic research in this field.

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Cadmium induces renal inflammation by activating the NLRP3 inflammasome through ROS/MAPK/NF-κB pathway in vitro and in vivo

Cited by 60 publications

References 64 publications

Polystyrene nanoplastics exacerbated lipopolysaccharide‐induced necroptosis and inflammation via the ROS/MAPK pathway in mice spleen

Polystyrene nanoplastics exacerbated lipopolysaccharide‐induced necroptosis and inflammation via the ROS/MAPK pathway in mice spleen

Clinical role of serum histone deacetylase 4 measurement in acute ischemic stroke: Relation to disease risk, severity, and prognosis

The Role of the NLRP3 Inflammasome in Mediating Glomerular and Tubular Injury in Diabetic Nephropathy

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