The orphan receptor Nur77 binds cytoplasmic LPS to activate the non-canonical NLRP3 inflammasome

Zhu, Fangrui; Ma, Juan; Li, Weitao; Liu, Qiannv; Qin, Xiwen; Qian, Ying; Wang, Chunlei; Zhang, Yan; Li, Yang; Jiang, Dong; Wang, Shuo; Xia, Pengyan

doi:10.1016/j.immuni.2023.03.003

Cited by 58 publications

(21 citation statements)

References 36 publications

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“…LPS is an endotoxin that acts as an important pathogenic component of the cell wall of Gram-negative bacteria [ 8 ]. Previous studies have shown that after the bacterial cell wall is damaged, LPS is released from the bacterial membrane, leading to the release of proinflammatory cytokines [ 22 ]. When it directly acts on the mammary epithelial cells of dairy cows, mastitis can be induced [ 7 , 9 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

CGA alleviates LPS-induced inflammation and milk fat reduction in BMECs through the NF-κB signaling pathway

Lyu,

Ji,

Che

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

CGA alleviates LPS-induced inflammation and milk fat reduction in BMECs through the NF-κB signaling pathway

Lyu,

Ji,

Che

et al. 2024

Heliyon

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“…The mechanistic activation of IECbound PRRs by their cognate ligands and how activation of these PRRs influence the various canonical and non-canonical signaling pathways requires further investigation. In this context, an orphan nuclear receptor, Nur77, has recently been shown to sense intracellular LPS, leading to non-canonical NLRP3 inflammasome activation via gasdermin-D (GSDMD) processing in macrophages (Zhu et al, 2023). Nur77 expression in macrophages was shown to increase upon treatment with various cognate TLR ligands, Frontiers in Cell and Developmental Biology frontiersin.org suggesting a possible crosstalk between the canonical and noncanonical signaling pathways of LPS sensing.…”

Section: Discussionmentioning

confidence: 99%

Know your neighbors: microbial recognition at the intestinal barrier and its implications for gut homeostasis and inflammatory bowel disease

Iyer

Erkert

Becker

2023

Front. Cell Dev. Biol.

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Intestinal epithelial cells (IECs) perform several physiological and metabolic functions at the epithelial barrier. IECs also play an important role in defining the overall immune functions at the mucosal region. Pattern recognition receptors (PRRs) on the cell surface and in other cellular compartments enable them to sense the presence of microbes and microbial products in the intestinal lumen. IECs are thus at the crossroads of mediating a bidirectional interaction between the microbial population and the immune cells present at the intestinal mucosa. This communication between the microbial population, the IECs and the underlying immune cells has a profound impact on the overall health of the host. In this review, we focus on the various PRRs present in different cellular compartments of IECs and discuss the recent developments in the understanding of their role in microbial recognition. Microbial recognition and signaling at the epithelial barrier have implications in the maintenance of intestinal homeostasis, epithelial barrier function, maintenance of commensals, and the overall tolerogenic function of PRRs in the gut mucosa. We also highlight the role of an aberrant microbial sensing at the epithelial barrier in the pathogenesis of inflammatory bowel disease (IBD) and the development of colorectal cancer.

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“…The mice with restraint stress-induced NASH received an intraperitoneal injection of lipopolysaccharide (LPS, 15 μg/kg; Sigma, St Louis, USA) [23] every three days for seven weeks. LPS was used as a positive control for NLRP3 activation to test whether restraint stress enhances NLRP3 signaling via a canonical or noncanonical pathway because LPS induces NLRP3 inflammasome activation via the canonical NF-κB pathway [24] and the noncanonical Caspase-11 or Caspase-4 pathway [25] . The animals were sacrificed after anaesthetization with ethyl ether at the end of the experiment.…”

Section: Methodsmentioning

confidence: 99%

Restraint stress promotes nonalcoholic steatohepatitis by regulating the farnesoid X receptor/NLRP3 signaling pathway

Yang,

Lv,

Lin

et al. 2023

ABBS

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Psychological stress promotes nonalcoholic steatohepatitis (NASH) development. However, the pathogenesis of psychological stress-induced NASH remains unclear. This study aims to explore the underlying mechanism of restraint stress-induced NASH, which mimics psychological stress, and to discover potential NASH candidates. Methionine choline deficient diet- and high fat diet-induced hepatosteatotic mice are subjected to restraint stress to induce NASH. The mice are administrated with Xiaoyaosan granules, NOD-like receptor family pyrin domain containing 3 (NLRP3) inhibitors, farnesoid X receptor (FXR) agonists, or macrophage scavengers. Pathological changes and NLRP3 signaling in the liver are determined. These results demonstrate that restraint stress promotes hepatic inflammation and fibrosis in hepatosteatotic mice. Restraint stress increases the expressions of NLRP3, Caspase-1, Gasdermin D, interleukin-1β, cholesterol 7α-hydroxylase, and sterol 12α-hydroxylase and decreases the expression of FXR in NASH mice. Xiaoyaosan granules reverse hepatic inflammation and fibrosis and target FXR and NLRP3 signals. In addition, inhibition of NLRP3 reduces the NLRP3 inflammasome and liver damage in mice with restraint stress-induced NASH. Elimination of macrophages and activation of FXR also attenuate inflammation and fibrosis by inhibiting NLRP3 signaling. However, NLRP3 inhibitors or macrophage scavengers fail to affect the expression of FXR. In conclusion, restraint stress promotes NASH-related inflammation and fibrosis by regulating the FXR/NLRP3 signaling pathway. Xiaoyaosan granules, NLRP3 inhibitors, FXR agonists, and macrophage scavengers are potential candidates for the treatment of psychological stress-related NASH.

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The orphan receptor Nur77 binds cytoplasmic LPS to activate the non-canonical NLRP3 inflammasome

Cited by 58 publications

References 36 publications

CGA alleviates LPS-induced inflammation and milk fat reduction in BMECs through the NF-κB signaling pathway

CGA alleviates LPS-induced inflammation and milk fat reduction in BMECs through the NF-κB signaling pathway

Know your neighbors: microbial recognition at the intestinal barrier and its implications for gut homeostasis and inflammatory bowel disease

Restraint stress promotes nonalcoholic steatohepatitis by regulating the farnesoid X receptor/NLRP3 signaling pathway

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