Crystals of monosodium urate monohydrate enhance lipopolysaccharide-induced release of interleukin 1β by mononuclear cells through a caspase 1-mediated process

2008 ◽  
Vol 68 (2) ◽  
pp. 273-278 ◽  
Author(s):  
E J Giamarellos-Bourboulis ◽  
M Mouktaroudi ◽  
E Bodar ◽  
J van der Ven ◽  
B-J Kullberg ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Gouty Arthritis ◽  
Underlying Mechanism ◽  
Monosodium Urate ◽  
Peripheral Blood Mononuclear ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Factor Α ◽  
Msu Crystals ◽  
Urate Crystals

Objective:Recent studies suggest that crystals of monosodium urate (MSU), deposited in joints of patients with acute gouty arthritis, activate the NACHT domain, leucine-rich repeat and pyrin domain-containing protein (NALP)3 inflammasome. In the present study we have investigated whether production of proinflammatory cytokines by crystals was exacerbated during costimulation with Toll-like receptor (TLR) ligands.Methods:Mononuclear cells of 22 healthy donors were stimulated by various concentrations of MSU crystals in the absence or presence of lipopolysaccharide (LPS), Pam3Cys and flagellin. Production of tumour necrosis factor α (TNFα), interleukin (IL)1β and IL6, as well as the intracellular concentrations of proIL1β were measured by ELISA. mRNA transcripts of TNFα and IL1β were assessed by real-time PCR. Stimulation experiments were also performed with peripheral blood mononuclear cells (PBMCs) of one patient carrying a NALP3 mutation.Results:MSU induced a moderate release of IL1β and IL6, but not of TNFα. Urate crystals amplified IL1β production stimulated by the TLR4 ligand LPS, while no synergy was apparent for IL6 production. In addition, no synergy between urate crystals and Pam3Cys (TLR2 ligand) or flagellin (TLR5 ligand) was apparent. The synergy between urate crystals and LPS was directed at the level of the NALP3 inflammasome, as it was present only when active IL1β was measured, but not at the level of IL1 mRNA or proIL1β. The synergy between LPS and MSU crystals ceased to exist in the presence of a caspase 1 inhibitor.Conclusions:MSU crystals act in synergy with LPS for the induction of enhanced release of IL1β. Increased cleavage of proIL1β by urate-activated caspase 1 is proposed as the underlying mechanism.

scholarly journals Effects of Modified Simiao Decoction on IL-1βand TNFαSecretion in Monocytic THP-1 Cells with Monosodium Urate Crystals-Induced Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ya-Fei Liu ◽  
Sheng-Hao Tu ◽  
Zhe Chen ◽  
Yu Wang ◽  
Yong-Hong Hu ◽  
...  
Keyword(s):  
Gouty Arthritis ◽  
Underlying Mechanism ◽  
Monosodium Urate ◽  
Future Studies ◽  
Treatment Groups ◽  
Chinese Herbal Formula ◽  
Chinese Herbal ◽  
Control Serum ◽  
Msu Crystals ◽  
Urate Crystals

Simiao pill, a Chinese herbal formula containing four herbs, has been used in the treatment of gouty arthritis for many years. The aim of this study was to explore the effects of modified Simiao decoction (MSD) on IL-1βand TNFαsecretion in monocytic THP-1 cells with monosodium urate (MSU) crystals-induced inflammation. The MSU crystals-induced inflammation model in THP-1 cells was successfully established by the stimulation of phorbol 12-myristate 13-acetate (PMA) and MSU crystals. Then, the MSD-derived serum or control serum extracted from rat was administered to different treatment groups. The morphology of MSU crystals and THP-1 cells was observed. IL-1βand TNFαprotein expression in supernatant of THP-1 cells were determined by ELISA. Our data demonstrated that MSU crystals induced time-dependent increase of IL-1βand TNFα. Moreover, MSD significantly decreased IL-1βrelease in THP-1 cells with MSU crystals-induced inflammation. These results suggest that MSD is promising in the treatment of MSU crystals-induced inflammation in THP-1 cells. MSD may act as an anti-IL-1 agent in treating gout. The underlying mechanism may be related to NALP3 inflammasome which needs to be validated in future studies.

Altered distribution and enhanced osteoclastogenesis of mucosal-associated invariant T cells in gouty arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (8) ◽  
pp. 2124-2134
Author(s):  
Young-Nan Cho ◽  
Hae-Seong Jeong ◽  
Ki-Jeong Park ◽  
Hyung-Seok Kim ◽  
Eun-Hee Kim ◽  
...  
Keyword(s):  
Cell Activation ◽  
Mononuclear Cells ◽  
Gouty Arthritis ◽  
Bone Destruction ◽  
Peripheral Blood Mononuclear ◽  
Mait Cells ◽  
Tnf Α ◽  
Mait Cell ◽  
Msu Crystals

Abstract Objective This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. Methods Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. Results Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. Conclusion This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.

Study on the Anti-Gout Activity of Chlorogenic Acid: Improvement on Hyperuricemia and Gouty Inflammation

2014 ◽  
Vol 42 (06) ◽  
pp. 1471-1483 ◽  
Author(s):  
Zhao-Qing Meng ◽  
Zhao-Hui Tang ◽  
Yun-Xia Yan ◽  
Chang-Run Guo ◽  
Liang Cao ◽  
...  
Keyword(s):  
Uric Acid ◽  
Chlorogenic Acid ◽  
Gouty Arthritis ◽  
Monosodium Urate ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Factor Α ◽  
Anti Inflammation ◽  
Necrosis Factor ◽  
Msu Crystals

Gout is a metabolic disorder associated with hyperuricemia resulting in the deposition of monosodium urate (MSU) crystals in joints and tissues. Lowering serum uric acid (Sur) levels and anti-inflammation are highly essential in treating gout. Chlorogenic acid (CA), as one of the most abundant polyphenols in the Chinese medicines, has been rarely reported to have an anti-gout effect. The model of potassium oxonate (PO)-induced hyperuricemia in mice and MSU crystal-induced inflammation in rats has been established in this study. The potential beneficial effects and mechanisms of CA on hyperuricemia and gouty arthritis were elucidated. The results demonstrated that CA significantly decreased the Sur level by inhibiting the xanthine oxidase (XOD) activity but not increasing the urinary uric acid (Uur) level. In addition, CA also exhibited the effect of suppressing paw swelling. Further investigation indicated that CA improved the symptoms of inflammation induced by MSU crystals by inhibiting the production of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The present study suggests that CA may have a considerable potential for development as an anti-gouty arthritis agent for clinical application.

Sirt1 ameliorates monosodium urate crystal–induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1674-1683 ◽  
Author(s):  
Lei Liu ◽  
Xiaoxia Zhu ◽  
Tianyi Zhao ◽  
Yiyun Yu ◽  
Yu Xue ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Macrophage Polarization ◽  
Polarization State ◽  
Underlying Mechanism ◽  
Joint Fluid ◽  
Raw 264.7 Cells ◽  
Acute Gout ◽  
Peripheral Blood Mononuclear ◽  
Sirt1 Expression ◽  
Msu Crystals

Abstract Objectives Acute gout is an inflammatory response to MSU crystals. In our previous research, Sirt1 was shown to have an effect in preventing acute gouty inflammation. In the current study, we aimed to investigate the underlying mechanism involving Sirt1 in acute gout. Methods The cytological changes and Sirt1 expression in the synovium were observed in patients with acute or intermittent gout. The effect of Sirt1 and its mechanism in gout were studied in macrophages, C57BL/6 mice and Sirt1+/− mice. Results Sirt1 expression was increased in the peripheral blood mononuclear cells (PBMCs) of patients with acute gout but not in the chronic tophus tissue. The arthritis score and numbers of inflammatory cells in injured paw tissue from murine gout models were upregulated in Sirt1+/− mice compared with wild-type mice. A PCR array of the paw tissue from murine gout models indicated that Sirt1 activation might attenuate MSU-induced inflammation by altering the polarization state of macrophages. Furthermore, in patients with acute gout, the phagocytosis of MSU crystals by a macrophage was found in a smear of the joint fluid and large amounts of macrophages were also found in the synovium. The activation of Sirt1 in gouty mice actually decreased the tendency toward M1 polarization. The inhibition of PI3K/Akt partially blocked the anti-inflammatory effect of Sirt1 and the translocation of STAT6, and phosphorylated STAT6 expression was decreased in RAW 264.7 cells treated with MSU crystals. Conclusion Our studies revealed that Sirt1 ameliorates MSU-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway.

scholarly journals HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Qiushi Huang ◽  
Wei Gao ◽  
Heng Mu ◽  
Ting Qin ◽  
Fan Long ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Mononuclear Cells ◽  
Stress Protein ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Peripheral Blood Mononuclear ◽  
Hsp60 Expression ◽  
Myd88 Signaling ◽  
Msu Crystals

Acute gout is an inflammatory response induced by monosodium urate (MSU) crystals. HSP60 is a highly conserved stress protein that acts as a cellular “danger” signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in gout. HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and molecular mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with intercritical gout (IG) or healthy controls (HCs). MSU crystals induced the expression and secretion of HSP60 in the macrophages. HSP60 knockdown or overexpression affects TLR4 and MyD88 expression, IκBα degradation, and the nuclear localization of NF-κB in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis mouse models pretreated with HSP60 vivo-morpholino, paw swelling, myeloperoxidase (MPO) activity, and inflammatory cell infiltration significantly decreased. Our study reveals that MSU crystal stimulates the expression of HSP60, which accelerates the TLR4-MyD88-NF-κB signaling pathway and exacerbates mitochondrial dysfunction.

scholarly journals Inhibition of Triggering Receptor Expressed on Myeloid Cell-1 Alleviates Acute Gouty Inflammation

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yonglong He ◽  
Qibin Yang ◽  
Xiuxiu Wang ◽  
Aimin Jia ◽  
Wenguang Xie ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Mononuclear Cells ◽  
Gouty Arthritis ◽  
Myeloid Cell ◽  
Monosodium Urate ◽  
Aseptic Inflammation ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Monocytes And Macrophages

Gout is a prevalent form of aseptic inflammation caused by the deposition of monosodium urate (MSU) crystals in joints or tissues. Triggering receptor expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on innate immune cells including granulocytes, monocytes, and macrophages. TREM-1 serves as a link between innate immunity and adaptive immunity, playing a crucial role in regulating inflammation and immune response. The purpose of this study was to investigate the potential role of TREM-1 in THP-1 cells and peripheral blood mononuclear cells (PBMCs) from patients with gouty arthritis (GA). In the current study, we found that the mRNA and protein levels of TREM-1 increased in PBMCs from GA patients and soluble TREM-1 in plasma as well. In addition, an increased level of TREM-1 was observed in THP-1 treated with monosodium urate (MSU) in vitro, along with upregulation of proinflammatory cytokines. Moreover, upon specific inhibition of TREM-1, Toll-like receptor 4 (TLR-4), and myeloid differentiation factor 88 (MyD88), the levels of MyD88 and proinflammatory cytokines were decreased after MSU challenge in THP-1 cells. Interestingly, inhibition of TLR-4 could enhance the effect of TREM-1 inhibitor in MSU-induced inflammation. Taken together, our findings suggested that TREM-1 could accelerate MSU-induced acute inflammation. Inhibition of TREM-1 may provide a new strategy for alleviating acute gouty inflammation.

scholarly journals HSP60 regulates monosodium urate crystal-induced inflammation by activating the TLR4-NF- κ B-MyD88 signaling pathway and disrupting mitochondrial function

2020 ◽  
Author(s):  
Wei Gao ◽  
Qiushi Huang ◽  
Ting Qin ◽  
Heng Mu ◽  
Fan Long ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mononuclear Cells ◽  
Stress Protein ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Peripheral Blood Mononuclear ◽  
Hsp60 Expression ◽  
Urate Crystal ◽  
Myd88 Signaling ◽  
Msu Crystals

Abstract Background Acute gout is an inflammatory response induced by monosodium urate (MSU) crystals. HSP60 is a highly conserved stress protein that acts as a cellular “danger” signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in the gout. Methods HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). Results HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with inter-critical gout (IG) or healthy controls (HCs). MSU crystals induced expression and secretion of HSP60 in the macrophages. HSP60 knockdown or over-expression affects TLR4 and MyD88 expression, IκBα degradation and the nuclear localization of NF-κB in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production, and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis and peritonitis mouse models pre-treated with HSP60 vivo-morpholino, paw swelling, ankle joint swelling, myeloperoxidase (MPO) activity and inflammatory cell infiltration significantly decreased. Conclusion Our study revealed that MSU crystal stimulates the expression of HSP60 which accelerates TLR4-MyD88-NF-κB signaling pathway and exacerbates mitochondrial dysfunction.

Biostatistical Analysis and Possible Forecasting of Relationship Between Uric Acid and Specific Laboratory Tests in Cases of Gouty Arthritis

2017 ◽  
Vol 68 (6) ◽  
pp. 1234-1241
Author(s):  
Adina Octavia Duse ◽  
Delia Berceanu Vaduva ◽  
Mirela Nicolov ◽  
Cristina Trandafirescu ◽  
Marcel Berceanu Vaduva ◽  
...  
Keyword(s):  
Uric Acid ◽  
Laboratory Tests ◽  
Gouty Arthritis ◽  
Main Diagnosis ◽  
Monosodium Urate ◽  
Glutamate Pyruvate ◽  
Metatarsophalangeal Joints ◽  
The Relationship ◽  
Biostatistical Analysis ◽  
Urate Crystals

Acute gouty arthritis represents an inflammatory response to microcrystals of monosodium urate that precipitate in joint tissues from supersaturated body fluids or are shed from preexisting articular deposits [1]. Gout is a metabolic disease characterized by recurrent episodes of arthritis associated with the presence of monosodium urate crystals in the tissue or synovial fluid during the attack.These forms of crystal-induced arthritis usually affect peripheral joints, including knee, ankle, wrist, and metacarpophalangeal and metatarsophalangeal joints. All of them may be associated with other inflammatory, endocrine diseases [2]. The present study was done to highlight the relationship between increased levels of uric acid and specific laboratory tests in order to possible forecast development of further disease in patients with gouty arthrithis.The present study was done on 34 patients hospitalized in Felix Hospital of Rehabilitation in 2015-2016, with age between 44 and 74, having the main diagnosis of gouty arthritis.We studied the following laboratory tests:urea and other related analysis, like uric acid, creatinine, cholesterol, glutamate pyruvate transaminase and glutamate oxalate transaminase.

scholarly journals Lipopolysaccharide stimulation test on cultured PBMCs assists the discrimination of cryopyrin-associated periodic syndrome from systemic juvenile idiopathic arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao-Yi Wu ◽  
Wen-Lang Fan ◽  
Ying-Ming Chiu ◽  
Huang-Yu Yang ◽  
Wen-I. Lee ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Periodic Syndrome ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Persistent Disease ◽  
Caspase 1 ◽  
Stimulation Tests

AbstractSystemic juvenile idiopathic arthritis (sJIA) and cryopyrin-associated periodic syndrome (CAPS) share many common manifestations. We aim to identify an applicable method to assist disease discrimination. Inflammatory cytokines were measured in the plasma of patients with CAPS, sJIA with persistent disease course and healthy controls. Supernatants collected from non-stimulated peripheral blood mononuclear cells (PBMCs) and those undergone inflammasome stimulation tests utilizing lipopolysaccharide (LPS) with and without adenosine triphosphate (ATP) were investigated. Inflammatory cytokines in patient plasma fail to differentiate sJIA from CAPS. PBMCs from sJIA secrets higher amount of IL-1β and IL-18 while CAPS PBMCs produces more caspase-1 without stimulation. IL-1β, IL-18, and caspase-1 were significantly elevated among CAPS PBMCs (all p < 0.05) upon LPS stimulation, but not when additional ATPs were provided. Levels of cytokines and PBMC responses to the stimulation assays were similar among all sJIA patients regardless of their history of macrophage activation syndrome. Unstimulated PBMC activities and the LPS inflammasome stimulation assay without exogenic ATPs can assist the differentiation of CAPS from sJIA with persistent disease course.

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