Role of NLRP3 Inflammasome in Lupus Nephritis and Therapeutic Targeting by Phytochemicals

Wu, Dantong; Ai, Lianjie; Sun, Yanping; Yang, Bing‐You; Chen, Sisi; Wang, Qiuhong; Kuang, Hai‐Xue

doi:10.3389/fphar.2021.621300

Cited by 11 publications

(7 citation statements)

References 123 publications

(127 reference statements)

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“…Moreover, NLRP3 inflammasome activation is induced by the NF-κB signaling pathway [ 61 ]. A growing number of studies have demonstrated the relationship between NLRP3 inflammasome activation and SLE [ 62 ]. Interestingly, inhibition of NLRP3 inflammasome activation ameliorates SLE disease in patients and SLE animal models [ 5 , 9 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice

et al. 2023

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Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response.

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Section: Discussionmentioning

confidence: 99%

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice

et al. 2023

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“…[41] Pyroptosis is a type of programmed cell death that is associated with the inflammasome. [42] LPS has been reported to induce NLRP3dependent pyroptosis by promoting ROS production in H9C2 cells. [43] Further reports pointed out that OTA could induce nephritis and renal fibrosis through the activation of NLRP3-dependent pyroptosis in MDCK cells and mice.…”

Section: Discussionmentioning

confidence: 99%

Taurine alleviates ochratoxin A‐induced pyroptosis in PK‐15 cells by inhibiting oxidative stress

Liu

et al. 2022

J Biochem & Molecular Tox

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Ochratoxin A (OTA) is one of the most harmful mycotoxins, which can cause multiple toxicological effects, especially nephrotoxicity in animals and humans. Taurine is an essential amino acid with various biological functions such as anti‐inflammatory and anti‐oxidation. However, the protective effect of taurine on OTA‐induced nephrotoxicity and pyroptosis had not been reported. Our results showed that OTA exposure induced cytotoxicity and oxidative stress in PK‐15 cells, including reactive oxygen species (ROS) accumulation, increased mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‐2), and decreased mRNA levels of catalase (CAT), glutathione peroxidase 1 (GPx1), and glutathione peroxidase 4 (GPx4). In addition, OTA treatment induced pyroptosis by increasing the expressions of pyroptosis‐related proteins NLRP3, GSDMD, Caspase‐1 P20, ASC, Pro‐caspase‐1, and IL‐1β. Meanwhile, taurine could alleviate OTA‐induced pyroptosis and cytotoxicity, as well as reduce ROS level, COX‐2, and iNOS mRNA levels, and increase the mRNA levels of the antioxidant enzyme in PK‐15 cells. Taken together, taurine alleviated OTA‐induced pyroptosis in PK‐15 cells by inhibiting ROS generation and altering the activity of antioxidant enzymes, thereby attenuating its nephrotoxicity.

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“…The NLRP3 inflammasome contribute to tissue damage in lupus nephritis [ 137 ]. Studies have shown that the NLRP3 inflammasome is upregulated in lupus nephritis patients and that its inhibition can ameliorate kidney injury in animal models of lupus nephritis [ 137 , 138 ]. Moreover, dysregulated lipid metabolism has also been implicated in the pathogenesis of lupus nephritis.…”

Section: The Impact Of Immunometabolic Dysregulation In Kidney Diseasementioning

confidence: 99%

The Interplay between Immune and Metabolic Pathways in Kidney Disease

Jiao

2023

Cells

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Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways, such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

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Role of NLRP3 Inflammasome in Lupus Nephritis and Therapeutic Targeting by Phytochemicals

Cited by 11 publications

References 123 publications

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice

Taurine alleviates ochratoxin A‐induced pyroptosis in PK‐15 cells by inhibiting oxidative stress

The Interplay between Immune and Metabolic Pathways in Kidney Disease

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