Enhanced p62 expression through impaired proteasomal degradation is involved in caspase-1 activation in monosodium urate crystal-induced interleukin-1  expression

The present study was undertaken to evaluate the therapeutic effects of Huzhang-Guizhi herb pair (HG), firstly included in Hu-Zhang Power documented in Taiping Shenghui Fang, on monosodium urate (MSU) crystals-induced gouty arthritis in rats. We found that pretreatment with HG in rats with gouty arthritis could significantly attenuate the ankle joint swelling, and this beneficial antigout effect might be mediated, at least in part, by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) production in synovial fluid as well as nuclear transcription factor-κB p65 (NF-κB p65) protein expression in synovial tissue. Moreover, metabonomic analysis demonstrated that 5 and 6 potential biomarkers associated with gouty arthritis in plasma and urine, respectively, which were mainly involved in energy metabolism, amino acid metabolism, and gut microbe metabolism, were identified. HG could reverse the pathological process of MSU-induced gouty arthritis through regulating the disturbed metabolic pathways. These results provided important mechanistic insights into the protective effects of HG against MSU-induced gouty arthritis in rats.

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EPS8 regulates an NLRP3 inflammasome-independent caspase-1 activation pathway in monosodium urate crystal-treated RAW264.7 macrophages

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2020.05.084 ◽

2020 ◽

Vol 530 (3) ◽

pp. 487-493 ◽

Cited By ~ 1

Author(s):

Jen-Pin Chuang ◽

Chuan-Yu Kao ◽

Jenq-Chang Lee ◽

Pin Ling ◽

Ming-Chei Maa ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Monosodium Urate ◽

Activation Pathway ◽

Caspase 1 ◽

Raw264.7 Macrophages ◽

Urate Crystal

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GPR30 negatively regulates inflammation in gout by inhibiting IL-1β production

10.21203/rs.3.rs-20679/v1 ◽

2020 ◽

Author(s):

Hongyan Qian ◽

Rongjuan Chen ◽

Shiju Chen ◽

Yan He ◽

Yuan Liu ◽

...

Keyword(s):

Aerobic Glycolysis ◽

Negative Regulation ◽

Activated Macrophages ◽

Monosodium Urate ◽

Caspase 1 ◽

Urate Crystal ◽

Nlrp3 Expression

Abstract Background: Gout is the most common inflammatory arthritis induced by monosodium urate crystal (MSU) precipitation.The incidence of gout attack was significantly higher in men than women, indicating the important role of oestrogen system in pathogenesis of gout, but the specific mechanisms underlying remained to be explored. GPR30, the newly defined estrogen receptor, had been proved participated in regulating inflammation in some diseases. As different estrogen receptors paly different role in inflammation regulation, how GPR30 was involved in the inflammation induced by MSU in gout was still unknown. Methods: In this work, we investigated the function of GPR30 in inflammation induced by MSU in cultured macrophages and in mouse model by using G-1(the agonist of GPR30). We further tested the expression of the TLR and NOD like receptor protein3 (NLRP3), which are the key receptor involved in pathogenesis of gout. ROS and cleaved-caspase-1 expression were also detected to confirm the regulation role in NLRP3 pathway. Seahorse analysis was used to detect the metabolism profile in macrophages by G-1 to investigate the mechanism of GPR30 in inflammation. The relative expression of GPR30 were detected according to the inflammation state to confirm the role of GPR30 in gout. Results: Negative regulation role of G-1 in IL-1β expression and NLRP3 expression were found both in vitro and in vivo. Moreover, the negative regulation of ROS production and NLRP3 as well as cleaved-caspase-1 expression were also found in G-1 stimulated macrophages. Our data also showed that G-1 inhibited aerobic glycolysis in LPS activated macrophages, which might be responsible for IL-1β and NLRP3 expression. Higher expression levels of GPR30 were found in patients with remitted gout inflammation. Conclusion: Together, our data suggested that GPR30 was involved in the negative inflammation regulation induced by MSU and high expression of GPR30 might contribute to part of the mechanism of inflammation remission of gout.

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Rebamipide Suppresses Monosodium Urate Crystal-Induced Interleukin-1β Production Through Regulation of Oxidative Stress and Caspase-1 in THP-1 Cells

Inflammation ◽

10.1007/s10753-015-0271-5 ◽

2015 ◽

Vol 39 (1) ◽

pp. 473-482 ◽

Cited By ~ 14

Author(s):

Seong-Kyu Kim ◽

Jung-Yoon Choe ◽

Ki-Yeun Park

Keyword(s):

Oxidative Stress ◽

Interleukin 1Β ◽

Monosodium Urate ◽

Caspase 1 ◽

Urate Crystal

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Faculty Opinions recommendation of Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726996092.793525670 ◽

2016 ◽

Author(s):

Frédéric Lioté

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Murine Models ◽

Innate Immune Responses ◽

Monosodium Urate ◽

Urate Crystal

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POS0132 IS THE INTERCRITICAL GOUT REALLY ASYMPTOMATIC? THE INFLAMMATORY ROLE OF THE SILENT URATE CRYSTAL DEPOSITION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1478 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 277.1-278

Author(s):

C. Diaz-Torne ◽

M. A. Ortiz ◽

S. Jeria Navarro ◽

A. Garcia-Gullien ◽

L. Sainz ◽

...

Keyword(s):

Risk Factors ◽

Whole Body ◽

Subclinical Inflammation ◽

Monosodium Urate ◽

Crystal Deposition ◽

Secretome Analysis ◽

Healthy Donors ◽

Cytokine Levels ◽

Urate Crystal ◽

Crystal Deposit

Background:Gout is the most prevalent inflammatory arthritis. Gout is chronic inflammatory deposition disease related to an increase of cardiovascular (CV) events and mortality. Subclinical chronic inflammation has been demonstrated in this patients but not its relation with the monosodium urate (MSU) crystal deposit size and the number of CV risk factors.Objectives:To study the subclinical inflammation in intercritical gout patients and its possible relation to the estimated size of the crystal deposition and the number of CV risk factors.Methods:To analyze subclinical inflammation we performed a secretome analysis and a cytokine and adiponektine plasma levels quantification (IL-1β, IL-18, IL-6, sIL-6R, TNFα, CXCL-5, RANTES, leptin, resistin and adiponectin) in a cohort of gout patients. As nowadays it is not feasible to determinate the whole body deposit of MSU crystals we created three different MSU crystal deposit size patient groups using an indirect clinical and analytical classification to estimate it. Then we compared cytokine levels between healthy donors and gout patients. We also compared cytokine levels between the different crystal size deposition groups and studied its association to the number of CV risk factors.Results:Ninety consecutive patients attending a Crystal Arthritis Unit were studied. Mean age was 68.27 (28-101) years. 81.1% were male. Clinical gout evolution was of 10.1±9.8 years. 77.5% were on urate lowering treatment. 24% had tophaceous gout. Mean uric acid was 6.3±2.1 mg/dl with 47.1% of them being on target. Hypertension was present in 68.9%, diabetes mellitus in 18.9%, dislipemia in 48.9%, BMI>30 in 32.9%, abdominal obesity in 50% and 16.1% suffered from ischemic heart disease. From the 102 molecules studied in the secretome analysis in 56 there was at least a 20% difference between donors group and any of the deposition groups. In 74% of them gout patients secreted lower levels. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in patients than in healthy donors. IL-18, sIL6-R, RANTES and CXCL5 levels were associated to the size of the crystal deposits. IL-18, sIL-6R, RANTES and leptin were higher in gout groups with CV risk factors. IL-18, sIL6-R, RANTES and leptin were higher in gout patients with no risk factors when compared to healthy donors with no risk factors. We found no differences when comparing urate lowering treated and non-treated patients.Conclusion:Our results demonstrate that some proinflammatory cytokines and metabolic proteins are raised in intercritical gout patients. Some of them are different from the flare/inflammasome expected ones. In some cytokines this elevation is related to the size of the monosodium urate crystal deposit and/or to the number of cardiovascular risk factors. This cytokine changes could help to explain the increase of the cardiovascular events in gout patients.Disclosure of Interests:Cesar Diaz-Torne Grant/research support from: Received a grant from Grünenthal, Maria Angels Ortiz: None declared, Sicylle Jeria Navarro: None declared, Andrea Garcia-Gullien: None declared, Lluis Sainz: None declared, Hector Corominas: None declared, Silvia Vidal: None declared

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Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis

Inflammation Research ◽

10.1007/s00011-021-01439-0 ◽

2021 ◽

Vol 70 (3) ◽

pp. 323-341

Author(s):

Yu Wang

Keyword(s):

Macrophage Polarization ◽

Gouty Arthritis ◽

Monosodium Urate ◽

Urate Crystal

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Drastic monosodium urate crystal dissolution with febuxostat and benzbromarone

Joint Bone Spine ◽

10.1016/j.jbspin.2021.105178 ◽

2021 ◽

Vol 88 (4) ◽

pp. 105178

Author(s):

Tristan Pascart ◽

Antoine Lefebvre ◽

Vincent Ducoulombier ◽

Fabio Becce ◽

Jean-François Budzik

Keyword(s):

Monosodium Urate ◽

Crystal Dissolution ◽

Urate Crystal

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Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Infection and Immunity ◽

10.1128/iai.00354-13 ◽

2013 ◽

Vol 81 (8) ◽

pp. 2997-3008 ◽

Cited By ~ 4

Author(s):

Wei Li ◽

Barry P. Katz ◽

Margaret E. Bauer ◽

Stanley M. Spinola

Keyword(s):

Nlrp3 Inflammasome ◽

Interleukin 1 ◽

Study Data ◽

Human Infection ◽

Haemophilus Ducreyi ◽

Inflammasome Activation ◽

Microbial Infection ◽

Content Type ◽

Ulcer Disease ◽

Caspase 1

ABSTRACTRecognition of microbial infection by certain intracellular pattern recognition receptors leads to the formation of a multiprotein complex termed the inflammasome. Inflammasome assembly activates caspase-1 and leads to cleavage and secretion of the proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-18, which help control many bacterial pathogens. However, excessive inflammation mediated by inflammasome activation can also contribute to immunopathology. Here, we investigated whetherHaemophilus ducreyi, a Gram-negative bacterium that causes the genital ulcer disease chancroid, activates inflammasomes in experimentally infected human skin and in monocyte-derived macrophages (MDM). AlthoughH. ducreyiis predominantly extracellular during human infection, several inflammasome-related components were transcriptionally upregulated inH. ducreyi-infected skin. Infection of MDM with live, but not heat-killed,H. ducreyiinduced caspase-1- and caspase-5-dependent processing and secretion of IL-1β. Blockage ofH. ducreyiuptake by cytochalasin D significantly reduced the amount of secreted IL-1β. Knocking down the expression of the inflammasome components NLRP3 and ASC abolished IL-1β production. Consistent with NLRP3-dependent inflammasome activation, blocking ATP signaling, K+efflux, cathepsin B activity, and lysosomal acidification all inhibited IL-1β secretion. However, inhibition of the production and function of reactive oxygen species did not decrease IL-1β production. Polarization of macrophages to classically activated M1 or alternatively activated M2 cells abrogated IL-1β secretion elicited byH. ducreyi. Our study data indicate thatH. ducreyiinduces NLRP3 inflammasome activation via multiple mechanisms and suggest that the heterogeneity of macrophages within human lesions may modulate inflammasome activation during human infection.

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