scholarly journals Bisphenol A disrupts inflammatory responses via Nod-like receptor protein 3 pathway in macrophages

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Hee-Weon Lee ◽  
Sang Keun Ha ◽  
Yoonsook Kim
Keyword(s):  
Bisphenol A ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Receptor Protein ◽  
Prostaglandin E ◽  
Inflammasome Activation ◽  
No Production ◽  
Dental Resins ◽  
Nlrp3 Inflammasome Activation ◽  
Mitogen Activated Protein

AbstractBisphenol A (BPA) is a harmful endocrine disruptor that is found in polycarbonate plastics such as plastic food containers and in epoxy resins such as dental resins. In the current study, we investigated the effect of BPA on function of inflammatory responses involving activation of Nod-like receptor protein 3 (NLRP3) inflammasome. Treatment with BPA decreased nitric oxide (NO) production and expression levels of inducible NO synthase (iNOS), prostaglandin E2 (PGE2), and cyclooxygenase (Cox)-2 in RAW 264.7 macrophages. BPA also suppressed activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B activity (NF-κB). BPA significantly down-regulated the secretion of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18. The decreased production of IL-1β and IL-18 induced by BPA was associated with inactivation of the activity of the NLRP3 inflammasome. Collectively, these data suggested that BPA could act as a disruptor of the inflammation activity by regulating the NF-κB/MAPK pathways and NLRP3 inflammasome activation.

scholarly journals Orientin Ameliorates LPS-Induced Inflammatory Responses through the Inhibitory of the NF-κB Pathway and NLRP3 Inflammasome

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qingfei Xiao ◽  
Zhihui Qu ◽  
Ying Zhao ◽  
Liming Yang ◽  
Pujun Gao
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Receptor Protein ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Nlrp3 Inflammasome Activation ◽  
Underlying Mechanisms

Inflammation is a complex response to diverse pathological conditions, resulting in negative rather than protective effects when uncontrolled. Orientin (Ori), a flavonoid component isolated from natural plants, possesses abundant properties. Thus, we aimed to discover the potential therapeutic effects of orientin on lipopolysaccharide- (LPS-) induced inflammation in RAW 264.7 cells and the underlying mechanisms. In our studies, we evaluated the effects of Ori on proinflammatory mediator production stimulated by LPS, including tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-18, and IL-1β, along with prostaglandin E2 (PGE2) and NO. Our data indicated that orientin dramatically inhibited the levels of these mediators. Consistent with these results, the expression levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also reduced. Further study demonstrated that such inhibitory effects of Ori were due to suppression of the nuclear factor-kappa B (NF-κB) pathway and nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3) inflammasome activation, which may contribute to its anti-inflammatory effects. Together, these findings show that Ori may be an effective candidate for ameliorating LPS-induced inflammatory responses.

scholarly journals Juglone Suppresses LPS-induced Inflammatory Responses and NLRP3 Activation in Macrophages

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3104 ◽  
Author(s):  
Nam-Hun Kim ◽  
Hong-Ki Kim ◽  
Ji-Hak Lee ◽  
Seung-Il Jo ◽  
Hye-Min Won ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Inflammasome Activation ◽  
No Production ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Inflammatory Cytokine Production ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome has been implicated in a variety of diseases, including atherosclerosis, neurodegenerative diseases, and infectious diseases. Thus, inhibitors of NLRP3 inflammasome have emerged as promising approaches to treat inflammation-related diseases. The aim of this study was to explore the effects of juglone (5-hydroxyl-1,4-naphthoquinone) on NLRP3 inflammasome activation. The inhibitory effects of juglone on nitric oxide (NO) production were assessed in lipopolysaccharide (LPS)-stimulated J774.1 cells by Griess assay, while its effects on reactive oxygen species (ROS) and NLRP3 ATPase activity were assessed. The expression levels of NLRP3, caspase-1, and pro-inflammatory cytokines (IL-1β, IL-18) and cytotoxicity of juglone in J774.1 cells were also determined. Juglone was non-toxic in J774.1 cells when used at 10 μM (p < 0.01). Juglone treatment inhibited the production of ROS and NO. The levels of NLRP3 and cleaved caspase-1, as well as the secretion of IL-1β and IL-18, were decreased by treatment with juglone in a concentration-dependent manner. Juglone also inhibited the ATPase activities of NLRP3 in LPS/ATP-stimulated J774.1 macrophages. Our results suggested that juglone could inhibit inflammatory cytokine production and NLRP3 inflammasome activation in macrophages, and should be considered as a therapeutic strategy for inflammation-related diseases.

scholarly journals Coixol Suppresses NF-κB, MAPK Pathways and NLRP3 Inflammasome Activation in Lipopolysaccharide-Induced RAW 264.7 Cells

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 894 ◽  
Author(s):  
Yusheng Hu ◽  
Qilyu Zhou ◽  
Tianlong Liu ◽  
Zhongjie Liu
Keyword(s):  
Nitric Oxide ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Receptor Protein ◽  
Raw 264.7 Cells ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Coixol, a plant polyphenol extracted from coix (Coix lachryma-jobi L.var.ma-yuen Stapf), has not been investigated for its anti-inflammatory effect. In this study, using a lipopolysaccharide (LPS)-induced macrophage cell model, we observed that coixol can effectively reduce the expression of interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthases (iNOS), and cyclooxygenase (COX)-2, but had no effect on the expression of the anti-inflammatory mediator IL-10. Furthermore, we found that coixol inhibits mitogen-activated protein kinases (MAPKs), nuclear transcription factor κ B (NF-κB) pathways, and NOD-like receptor protein (NLRP) 3 inflammasome activation. In conclusion, the present study demonstrates that coixol exerts certain anti-inflammatory effects by inhibiting the expression of pro-inflammatory mediators in vitro. The mechanism of this effect was in part related to its ability to inhibit the activation of NF-κB, MAPKs pathways, and NLRP3 inflammasome.

Anti-Inflammatory Activity of Lobaric Acid via Suppressing NF-κB/MAPK Pathways or NLRP3 Inflammasome Activation

Planta Medica ◽  
2018 ◽  
Vol 85 (04) ◽  
pp. 302-311 ◽  
Author(s):  
Hee-Weon Lee ◽  
JinWook Kim ◽  
Joung-Han Yim ◽  
Hong-Kum Lee ◽  
Suhkneung Pyo
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Inflammasome Activation ◽  
Mapk Pathways ◽  
Nlrp3 Inflammasome Activation ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Necrosis Factor

Lobaric acid (LA) is a constituent of the lichen Stereocaulon alpinum. LA has multiple biological activities, including antibacterial and antioxidant ones. The purpose of this study was to investigate the effect of LA and its mechanism on lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Macrophages were pretreated with different concentrations of LA (0.2 – 20 µM), followed by LPS stimulation. LA treatment of LPS stimulated macrophages decreased their nitric oxide production and the expression of cyclooxygenase-2 and prostaglandin E2. LA also significantly reduced the production of tumor necrosis factor-α and interleukin (IL)-6 by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB). Additionally, LA inhibited the production of IL-1β and IL-18, as well as caspase-1 maturation, by inhibition of NLRP3 inflammasome activation in LPS/ATP-stimulated cells. These results strongly suggest that LA could inhibit inflammation by downregulating NF-κB/MAPK pathways and NLRP3 inflammasome activation in activated macrophages. These results reveal a new therapeutic approach to modulate inflammatory diseases linked to deregulated inflammasome activities.

scholarly journals Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1948
Author(s):  
Yu-Chi Cheng ◽  
Li-Wen Chu ◽  
Jun-Yih Chen ◽  
Su-Ling Hsieh ◽  
Yu-Chin Chang ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Purinergic Receptor ◽  
Receptor Protein ◽  
Ros Generation ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

Diabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyroptosis in diabetes. Schwann cell dysfunction further promotes DPN progression. Loganin has been shown to have antioxidant and anti-inflammatory neuroprotective activities. This study evaluated the neuroprotective effect of loganin on high-glucose (25 mM)-induced rat Schwann cell line RSC96 injury, a recognized in vitro cell model of DPN. RSC96 cells were pretreated with loganin (0.1, 1, 10, 25, 50 μM) before exposure to high glucose. Loganin’s effects were examined by CCK-8 assay, ROS assay, cell death assay, immunofluorescence staining, quantitative RT–PCR and western blot. High-glucose-treated RSC96 cells sustained cell viability loss, ROS generation, NF-κB nuclear translocation, P2 × 7 purinergic receptor and TXNIP (thioredoxin-interacting protein) expression, NLRP3 inflammasome (NLRP3, ASC, caspase-1) activation, IL-1β and IL-18 maturation and gasdermin D cleavage. Those effects were reduced by loganin pretreatment. In conclusion, we found that loganin’s antioxidant effects prevent RSC96 Schwann cell pyroptosis by inhibiting ROS generation and suppressing NLRP3 inflammasome activation.

scholarly journals SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pan Pan ◽  
Miaomiao Shen ◽  
Zhenyang Yu ◽  
Weiwei Ge ◽  
Keli Chen ◽  
...  
Keyword(s):  
Lung Injury ◽  
Nlrp3 Inflammasome ◽  
Cultured Cells ◽  
Inflammatory Responses ◽  
Specific Inhibitor ◽  
Inflammasome Activation ◽  
N Protein ◽  
Distinct Mechanism ◽  
Nlrp3 Inflammasome Activation ◽  
Proinflammatory Responses

AbstractExcessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.

Psidium guajava Flavonoids Prevent NLRP3 Inflammasome Activation and Alleviate the Pancreatic Fibrosis in a Chronic Pancreatitis Mouse Model

2021 ◽  
Vol 49 (08) ◽  
pp. 2001-2015
Author(s):  
Guixian Zhang ◽  
Liming Tang ◽  
Hongbin Liu ◽  
Dawei Liu ◽  
Manxue Wang ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Psidium Guajava ◽  
Pancreatic Fibrosis ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

Chronic pancreatitis (CP) is a multifactorial, inflammatory syndrome characterized by acinar atrophy and fibrosis. Activation of NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome is a central mediator of multiple chronic inflammatory responses and chronic fibrosis including pancreatic fibrosis in CP. The Psidium guajavaleaf is widely used in traditional medicine for the treatment of chronic inflammation, but the anti-inflammatory effect of Psidium guajavaleaf on CP has not yet been revealed. In this study, we investigated whether the extract of total flavonoids from Psidium guajava leaves (TFPGL) plays a therapeutic mechanism on CP through NLRP3 inflammasome signaling pathway in a mouse CP model. The H&E and acid-Sirius red staining indicted that TFPGL attenuated the inflammatory cell infiltration and fibrosis significantly. The results of immunohistological staining, western blot and RT-qPCR showed that the expressions of NLRP3 and caspase-1 were significantly increased in the CP model group, while TFPGL significantly decreased the NLRP3 and caspase-1 expression at both the gene and protein levels. Moreover, ELISA assay was used to examine the levels of NLRP3 inflammasome target genes, such as caspase-1, IL-1[Formula: see text] and IL-18. We found that TFPGL treatment decreased the expression of caspase-1, IL-1[Formula: see text] and IL-18, which is critical for the NLRP3 inflammasome signaling pathway and inflammation response significantly. These results demonstrated that TFPGL attenuated pancreatic inflammation and fibrosis via preventing NLRP3 inflammasome activation and TFPGL can be used as a potential therapeutic agent for CP.

scholarly journals Role of NLRP3 inflammasome in the development of bladder pain syndrome interstitial cystitis

2019 ◽  
Vol 11 ◽  
pp. 175628721881803 ◽  
Author(s):  
Karol Borys Tudrej ◽  
Tomasz Piecha ◽  
Małgorzata Kozłowska-Wojciechowska
Keyword(s):  
Interstitial Cystitis ◽  
Nlrp3 Inflammasome ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Bladder Epithelium ◽  
Bladder Pain ◽  
Bladder Inflammation ◽  
Nlrp3 Inflammasome Activation

Although it has been proposed that NOD-like receptor protein 3 (NLRP3) inflammasome activation may have an important contribution to the onset of bladder pain syndrome/interstitial cystitis (BPS/IC), as of today there is still insufficient evidence to accept or to reject this hypothesis. However, taking into consideration that inflammasomes have been already shown as important mediators of cyclophosphamide-induced bladder inflammation and that some studies have also revealed human bladder epithelium expresses high levels of NLRP3, such a hypothesis seems to be reasonable. The purpose of this review is to discuss a scenario that NLRP3 inflammasome is a crucial player in the development of this disease. Identification of a novel mediator of bladder inflammation and pain could lead to emerging new therapeutic strategy and the first causative therapy.

scholarly journals ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia/Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Letteria Minutoli ◽  
Domenico Puzzolo ◽  
Mariagrazia Rinaldi ◽  
Natasha Irrera ◽  
Herbert Marini ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Ion Homeostasis ◽  
Inflammasome Activation ◽  
Mortality And Morbidity ◽  
Arterial Blood ◽  
Nlrp3 Inflammasome Activation

Ischemia and reperfusion (I/R) causes a reduction in arterial blood supply to tissues, followed by the restoration of perfusion and consequent reoxygenation. The reestablishment of blood flow triggers further damage to the ischemic tissue through reactive oxygen species (ROS) accumulation, interference with cellular ion homeostasis, and inflammatory responses to cell death. In normal conditions, ROS mediate important beneficial responses. When their production is prolonged or elevated, harmful events are observed with peculiar cellular changes. In particular, during I/R, ROS stimulate tissue inflammation and induce NLRP3 inflammasome activation. The mechanisms underlying the activation of NLRP3 are several and not completely elucidated. It was recently shown that NLRP3 might sense directly the presence of ROS produced by normal or malfunctioning mitochondria or indirectly by other activators of NLRP3. Aim of the present review is to describe the current knowledge on the role of NLRP3 in some organs (brain, heart, kidney, and testis) after I/R injury, with particular regard to the role played by ROS in its activation. Furthermore, as no specific therapy for the prevention or treatment of the high mortality and morbidity associated with I/R is available, the state of the art of the development of novel therapeutic approaches is illustrated.

Sign in / Sign up

Export Citation Format

Share Document