Acetoacetate is a trigger of NLRP3 inflammasome activation in bovine peripheral blood mononuclear cells

Onizawa, Yuri; Katoh, Taiga; Miura, Reiko; Konda, Kunitoshi; Noguchi, Toshihiro; Iwata, Hisataka; Kuwayama, Takehito; Hamano, Seizo; Shirasuna, Koumei

doi:10.1016/j.vetimm.2021.110370

Cited by 5 publications

(4 citation statements)

References 53 publications

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“…In addition, tyrosine along with phenylalanine in serum has been implicated in the activation of the immune system in other diseases [ 55 , 56 ]. Finally, β-hydroxybutyrate and acetoacetate have been associated with inflammation by modulating NLRP3 inflammasome, which has been associated to OA pathogenesis [ 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Synovial tissue metabolomic profiling reveal biomarkers of synovial inflammation in patients with osteoarthritis

Murillo-Saich¹,

Coras²,

Meyer³

et al. 2022

Osteoarthritis and Cartilage Open

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Section: Discussionmentioning

confidence: 99%

Synovial tissue metabolomic profiling reveal biomarkers of synovial inflammation in patients with osteoarthritis

Murillo-Saich¹,

Coras²,

Meyer³

et al. 2022

Osteoarthritis and Cartilage Open

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“…Metabolomic profiling in blood plasma has been used to identify metabolites that could help diagnose RBC syndrome [ 48 , 49 ]. Researchers reported lower levels of bile acids and kynurenine, and a total of 17 metabolites in the blood plasma of RBCs that were not present in control cows [ 49 ].…”

Section: New Omics and Technologies To Understand The Rbc Syndromementioning

confidence: 99%

“…Researchers reported lower levels of bile acids and kynurenine, and a total of 17 metabolites in the blood plasma of RBCs that were not present in control cows [ 49 ]. Imbalances of ketone bodies, such as acetoacetate (AcAc) and ß-hydroxybutyrate (BHB), have been associated with abnormal inflammatory conditions in RBCs throughout the activation of the NLRP3 inflammasome, which regulates sterile inflammation and IL-1β secretion [ 48 ]. Inflammation plays a role in the physiology and pathophysiology of pregnancy, and any disruption in immune function could lead to infertility, spontaneous abortion, and recurrent pregnancy loss [ 50 , 51 ].…”

Section: New Omics and Technologies To Understand The Rbc Syndromementioning

confidence: 99%

“…In a similar syndrome observed in humans, in recurrent pregnancy loss, both IL-1β and NLRP3 inflammasomes are expressed at higher levels in endometrial human tissues [ 53 ]. Then, NLRP3 inflammasome activation and IL-1β overproduction in uterine tissue might be proposed as tentative causes of RBC syndrome [ 48 ]. According to the reviewed literature, an inflammatory response could be associated with RBC syndrome, and perhaps anti-inflammatory therapy might partially resolve this syndrome.…”

Section: New Omics and Technologies To Understand The Rbc Syndromementioning

confidence: 99%

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Current Insights in the Repeat Breeder Cow Syndrome

Marı́n

Arias

2023

Animals

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Cows can have difficulties becoming pregnant, and in certain cases, these reproductive failures do not have an evident cause. Furthermore, when these failures are repeated three or more times with estrous cycles of normal duration and in the absence of evident clinical signs, it is considered repeat breeder cow (RBC) syndrome. A substantive incidence of RBC syndrome has been reported all over the world, which severely affects the farm economy. This paper reviews those studies particularly focused on RBC syndrome from 2000 to 2023 but also includes consolidated information until this date. Hormonal imbalances, undetectable oviductal or uterine defects, or poor oocyte or embryo quality have been reported as causes of RBC syndrome, while subclinical endometritis has been considered a relevant causal agent. However, it is unresolved why this condition is recurrent in certain animals, despite the implementation of corrective management actions or treatments. Recent studies evaluate the putative role of certain genes, factors, hormones, or proteins in the pathogenesis of RBC syndrome. Numerous risk factors contribute to the appearance of this syndrome, and some of them could be mitigated to partially prevent this infertility, while others cannot be changed. Due to the complexity of this syndrome, it is important to increase knowledge about the mechanisms involved, develop new diagnostic tools to differentiate causal agents, and implement new treatments to restore fertility. There is consensus about the huge repercussions of this syndrome on farm profitability, but further studies are now needed to describe its economic impact.

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New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation

kodi,

Sankhe,

Gopinathan

et al. 2024

J Neuroimmune Pharmacol

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Inflammasomes are important modulators of inflammation. Dysregulation of inflammasomes can enhance vulnerability to conditions such as neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Among various inflammasomes, Nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) is the best-characterized inflammasome related to inflammatory and neurodegenerative diseases. NLRP3 is an intracellular sensor that recognizes pathogen-associated molecular patterns and damage-associated patterns resulting in the assembly and activation of NLRP3 inflammasome. The NLRP3 inflammasome includes sensor NLRP3, adaptor apoptosis-associated speck-like protein (ASC), and effector cysteine protease procaspase-1 that plays an imperative role in caspase-1 stimulation which further initiates a secondary inflammatory response. Regulation of NLRP3 inflammasome ameliorates NLRP3-mediated diseases. Much effort has been invested in studying the activation, and exploration of specific inhibitors and epigenetic mechanisms controlling NLRP3 inflammasome. This review gives an overview of the established NLRP3 inflammasome assembly, its brief molecular mechanistic activations as well as a current update on specific and non-specific NLRP3 inhibitors that could be used in NLRP3-mediated diseases. We also focused on the recently discovered epigenetic mechanisms mediated by DNA methylation, histone alterations, and microRNAs in regulating the activation and expression of NLRP3 inflammasome, which has resulted in a novel method of gaining insight into the mechanisms that modulate NLRP3 inflammasome activity and introducing potential therapeutic strategies for CNS disorders. Graphical Abstract "Image missing"

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Acetoacetate is a trigger of NLRP3 inflammasome activation in bovine peripheral blood mononuclear cells

Cited by 5 publications

References 53 publications

Synovial tissue metabolomic profiling reveal biomarkers of synovial inflammation in patients with osteoarthritis

Synovial tissue metabolomic profiling reveal biomarkers of synovial inflammation in patients with osteoarthritis

Current Insights in the Repeat Breeder Cow Syndrome

New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation

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