Sensing soluble uric acid by Naip1-Nlrp3 platform

Braga, Tárcio Teodoro; Davanso, Mariana Rodrigues; Mendes, Davi; Souza, Tiago Antônio de; Cruz, Mário Costa; Hiyane, Meire Ioshie; Lima, Dhêmerson Souza de; Nunes, Vinicius; Giarola, Juliana de Fátima; Souto, Dênio Emanuel Pires; Próchnicki, Tomasz; Lauterbach, Mario A.; Biscaia, Stellee Marcela Petris; Freitas, Rilton Alves de; Curi, Rui; Pontillo, Alessandra; Latz, Eicke; Câmara, Niels Olsen Saraiva

doi:10.1038/s41419-021-03445-w

Cited by 19 publications

(16 citation statements)

References 77 publications

(42 reference statements)

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“…However, all in vivo studies are based on low serum UA levels of 2–5 mg/dL that are not considered as HU in humans. In vitro studies using crystalline UA (cUA) consistently report pro-inflammatory and cytotoxic effects in murine and human monocytes and macrophages [ 17 , 18 , 19 , 20 , 21 ], similar to what has been broadly reported with other crystalline particles [ 22 , 23 , 24 ]. While these effects likely attribute to UA microcrystal contaminations, recent evidence indicates that microcrystal-free soluble UA (sUA) preparations rather attenuate pro-inflammatory effects of human monocytes [ 25 ].…”

Section: Introductionmentioning

confidence: 65%

“…Several in vitro studies reported that UA triggers the release of pro-inflammatory mediators, including NLRP3 inflammasome-mediated IL-1β production in lipopolysaccharide (LPS) and monosodium urate (MSU) crystal-stimulated murine and human monocytes and macrophages [ 17 , 18 , 19 , 20 , 21 ]. However, such studies prepared UA by pre-warming UA powder at 37 °C in culture medium, a preparation method that does not fully solubilize UA so that UA microcrystals remain as contaminants.…”

Section: Discussionmentioning

confidence: 99%

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Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

Gnemmi

et al. 2022

Cells

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Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incompletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation. In vitro, 10 mg/dL sUA decreased reactive oxygen species and interleukin-6 production in macrophages, while enhancing fatty acid oxidation as compared with a physiological concentration of 5 mg/dL sUA or medium. In transgenic mice, asymptomatic HU of 7–10 mg/dL did not affect post-ischemic AKI/AKD but accelerated the recovery of kidney excretory function on day 14. Improved functional outcome was associated with better tubular integrity, less peritubular inflammation, and interstitial fibrosis. Mechanistic studies suggested that HU shifted macrophage polarization towards an anti-inflammatory M2-like phenotype characterized by expression of anti-oxidative and metabolic genes as compared with post-ischemic AKI-chronic kidney disease transition in mice without HU. Our data imply that asymptomatic HU acts as anti-oxidant on macrophages and tubular epithelial cells, which endorses the recovery of kidney function and structure upon AKI.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

Gnemmi

et al. 2022

Cells

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“…Although HUA is considered to be an adverse factor in cardiovascular events, the general treatment of asymptomatic HUA to reduce cardiovascular risk is not recommended. 33 This study is the first to assess the mediating effects of chronic inflammation in PBMCs on the association between high SUA levels and coronary calcium deposition. Chronic inflammation is recognized as the major underlying cause of many pathologies including cardiovascular and cerebrovascular events, with mononuclear cells and cytokines playing a critical role in the initial stages of these diseases.…”

Section: Discussionmentioning

confidence: 99%

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

Wang¹,

Liu²,

Qi³

et al. 2022

JIR

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Background Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China. Methods A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan–Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects. Results Based on the first year of follow-up data analysis, the elevation of SUA levels ( P <0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P <0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups. Conclusion Taken together, the findings in this study indicate that high SUA levels ( P <0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.

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“…However, it remains unclear how intracellular uric acid is recognized and activates signaling pathways. Recently, NAIP1 was reported to directly recognize intracellular uric acid and induce the activation of NLRP3 in mice [104]. However, the binding of uric acid with human NAIP1 is weak [104], so the effect of uric acid may be caused by other molecules in humans.…”

Section: Inflammasomementioning

confidence: 99%

Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

Kimura

Tsukui

Kono

2021

IJMS

168

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Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

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Sensing soluble uric acid by Naip1-Nlrp3 platform

Cited by 19 publications

References 77 publications

Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

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