Elaidic acid induced NLRP3 inflammasome activation via ERS-MAPK signaling pathways in Kupffer cells

2022 ◽  
Vol 1867 (1) ◽  
pp. 159061
Author(s):  
Hui Liu ◽  
Bo Nan ◽  
Chaoyue Yang ◽  
Xuenan Li ◽  
Haiyang Yan ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Kupffer Cells ◽  
Elaidic Acid ◽  
Nlrp3 Inflammasome ◽  
Mapk Signaling ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Mapk Signaling Pathways

scholarly journals Mycotoxin Zearalenone Attenuates Innate Immune Responses and Suppresses NLRP3 Inflammasome Activation in LPS-Activated Macrophages

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 593
Author(s):  
Po-Yen Lee ◽  
Ching-Chih Liu ◽  
Shu-Chi Wang ◽  
Kai-Yin Chen ◽  
Tzu-Chieh Lin ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Adverse Effects ◽  
Signaling Pathways ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Mammalian Species ◽  
Inflammasome Activation ◽  
Amino Terminal ◽  
Proinflammatory Mediators ◽  
Nlrp3 Inflammasome Activation

Zearalenone (ZEA) is a mycotoxin that has several adverse effects on most mammalian species. However, the effects of ZEA on macrophage-mediated innate immunity during infection have not been examined. In the present study, bacterial lipopolysaccharides (LPS) were used to induce the activation of macrophages and evaluate the effects of ZEA on the inflammatory responses and inflammation-associated signaling pathways. The experimental results indicated that ZEA suppressed LPS-activated inflammatory responses by macrophages including attenuating the production of proinflammatory mediators (nitric oxide (NO) and prostaglandin E2 (PGE2)), decreased the secretion of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), inhibited the activation of c-Jun amino-terminal kinase (JNK), p38 and nuclear factor-κB (NF-κB) signaling pathways, and repressed the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. These results indicated that mycotoxin ZEA attenuates macrophage-mediated innate immunity upon LPS stimulation, suggesting that the intake of mycotoxin ZEA-contaminated food might result in decreasing innate immunity, which has a higher risk of adverse effects during infection.

Adiponectin inhibits palmitic acid-induced NLRP3 inflammasome activation in hepatocytes through AMPK-JNK/ErK1/2-NFκB/ROS signaling pathways

2020 ◽  
Author(s):  
Zhixia Dong ◽  
Qian Zhuang ◽  
Xin Ye ◽  
Min Ning ◽  
Shan Wu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Palmitic Acid ◽  
Signaling Pathways ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Ros Production ◽  
Wild Type ◽  
Nlrp3 Inflammasome Activation

Abstract Background Adiponectin, an adipose-derived adipokine, possesses a hepatoprotective role in various liver disorders. Inflammasome activation has been recognized to play a major role during the progression of non-alcoholic fatty liver diseases (NAFLD). However, the effect of adiponectin on NLRP3 inflammasome activation in liver and the exact mechanism remains largely unclear. Here, we assessed the effect of adiponectin on NLRP3 inflammasome activation and its potential molecular mechanisms through both in vivo and in vitro experiments. Methods Male adiponectin-knockout (adiponectin-KO) mice and C57BL/6 (wild-type) mice were fed a high-fat-diet (HFD) for 12 weeks as an in vivo model of non-alcoholic steatohepatitis (NASH). Serum biochemical markers, liver histology and inflammasome-related gene and protein expression were determined. In addition, the hepatocytes isolated from SD rats were exposed to palmitic acid(PA) in the absence or presence of adiponectin and/or AMPK inhibitor. The activation of NLRP3 inflammasome was assessed by mRNA and protein expression. Furthermore, ROS production and related signaling pathways were also evaluated. Results In the in vivo experiments, we found that adiponectin deficiency mice fed with HFD presented excessive hepatic steatosis with increased NLRP3 inflammasome activation compared to wild-type mice. Moreover, the expression levels of NLRP3 inflammasome activation pathway molecules (NFκB and ROS) were upregulated, while the phosphorylation levels of AMPK, JNK and Erk1/2 were downregulated in adiponectin-knockout mice compared with wild-type mice. In the in vitro study, PA significantly promoted NLRP3 inflammasome activation in hepatocytes. Additionally, PA increased lipid droplet deposition, NF-kB signaling and ROS production, while adiponectin could abolish PA-mediated NLRP3 inflammasome activation and decrease ROS production, which was reversed by AMPK inhibitor (compound C). The results indicated that the inhibitory effect of adiponectin on PA-mediated NLRP3 inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS signaling pathway. Conclusion Adiponectin inhibited PA-mediated NLRP3 inflammasome activation in hepatocytes. Adiponectin analogs or AMPK agonists could serve as a potential novel agent for preventing or delaying the progression of NASH and NAFLD.

scholarly journals Staphylococcal Enterotoxin A Induces Intestinal Barrier Dysfunction and Activates NLRP3 Inflammasome via NF-κB/MAPK Signaling Pathways in Mice

Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 29
Author(s):  
Chunmei Liu ◽  
Kunmei Chi ◽  
Meng Yang ◽  
Na Guo
Keyword(s):  
Signaling Pathways ◽  
Nlrp3 Inflammasome ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Staphylococcal Enterotoxin ◽  
Foodborne Diseases ◽  
Staphylococcal Enterotoxin A ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Mapk Signaling Pathways

Staphylococcal enterotoxin A (SEA), the toxin protein secreted by Staphylococcus aureus, can cause staphylococcal food poisoning outbreaks and seriously threaten global public health. However, little is known about the pathogenesis of SEA in staphylococcal foodborne diseases. In this study, the effect of SEA on intestinal barrier injury and NLRP3 inflammasome activation was investigated by exposing BALB/c mice to SEA with increasing doses and a potential toxic mechanism was elucidated. Our findings suggested that SEA exposure provoked villi injury and suppressed the expression of ZO-1 and occludin proteins, thereby inducing intestinal barrier dysfunction and small intestinal injury in mice. Concurrently, SEA significantly up-regulated the expression of NLRP3 inflammasome-associated proteins and triggered the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in jejunum tissues. Notably, selective inhibitors of MAPKs and NF-κB p65 ameliorated the activation of NLRP3 inflammasome stimulated by SEA, which further indicated that SEA could activate NLRP3 inflammasome through NF-κB/MAPK pathways. In summary, SEA was first confirmed to induce intestinal barrier dysfunction and activate NLRP3 inflammasome via NF-κB/MAPK signaling pathways. These findings will contribute to a more comprehensive understanding of the pathogenesis of SEA and related drug-screening for the treatment and prevention of bacteriotoxin-caused foodborne diseases via targeting specific pathways.

Paeonol reduces IL-β production by inhibiting the activation of nucleotide oligomerization domain-like receptor protein-3 inflammasome and nuclear factor-κB in macrophages

2021 ◽  
pp. 1-9
Author(s):  
Gang Chen ◽  
Tingwang Guo ◽  
Lin Yang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Dna Binding Activity ◽  
Nlrp3 Inflammasome Activation ◽  
Nucleotide Oligomerization

Interleukin-1β, a key cytokine in gouty inflammation, is precisely regulated by the NLRP3 inflammasome and NF-κB. Our previous study demonstrated that paeonol suppressed IL-1β production in rats with monosodium urate (MSU)-induced arthritis. Whether NLRP3 inflammasome or NF-κB is responsible for the anti-inflammatory effect of paeonol remains unclear. In this study, J774A.1 cells induced by lipopolysaccharide (LPS) plus MSU, was used to investigate the effect of paeonol on NLRP3 inflammasome activation, and J774A.1 cells induced by LPS alone were used to investigate the effect of paeonol on NF-κB activation. In J774A.1 cells induced by LPS plus MSU, paeonol decreased the levels of IL-1β and caspase-1 and reduced the MSU-induced interaction of pro-caspase-1 and apoptosis-associated speck-like protein containing caspase recruitment domain (ASC), but did not affect the levels of pro-IL-1β and pro-caspase-1. In J774A.1 cells induced by LPS alone, paeonol reduced the levels of IL-1β, NLRP3, p-IKK, p-IκBα, and p-p65, but did not affect ASC levels. Paeonol also promoted the content of IκBα and retained more p65 in the cytoplasm. Furthermore, paeonol reduced the DNA-binding activity of p65 and lowered the levels of p-JNK, p-ERK, and p-p38. These results suggest that paeonol inhibits IL-1β production by inhibiting the activation of NLRP3 inflammasome, NF-κB, and MAPK signaling pathways.

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