scholarly journals Neutrophil extracellular trap clearance by synovial macrophages in gout

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Ji Hye Jeong ◽  
Su Jin Choi ◽  
Soo Min Ahn ◽  
Ji Seon Oh ◽  
Yong-Gil Kim ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Gouty Arthritis ◽  
Immunological Response ◽  
Neutrophil Extracellular Trap ◽  
Extracellular Traps ◽  
Sytox Green ◽  
Anti Inflammatory ◽  
Msu Crystals

Abstract Background Monosodium urate (MSU) crystals, i.e., the central etiological factors in gouty arthritis, induce the formation of neutrophil extracellular traps (NETs). We investigated whether synovial macrophages could clear NETs as a self-resolution mechanism in acute gouty arthritis. Methods Synovial fluid mononuclear cells (SFMCs) were incubated with NETs induced by MSU crystals. NET engulfment was determined based on neutrophil elastase (NE), myeloperoxidase (MPO), and SYTOX Green signals within synovial fluid CD14+ cells. In addition, the correlations between CD14+ cells, MPO-dsDNA complexes, and expression of pro- and anti-inflammatory cytokines were analyzed in the synovial fluid CD14+ macrophages of patients with gouty arthritis. Results Synovial fluid CD14+ macrophages significantly engulfed the MSU crystal-induced NETs, as evidenced by the alteration in SYTOX Green intensity or the presence of NE and MPO in the cytoplasm of CD14+ cells. The proportion of CD14+ macrophages was significantly and inversely correlated with levels of MPO-dsDNA complex in the synovial fluid of gout patients. Synovial fluid CD14+ macrophages cultured with NETs did not show a significant induction in pro- and anti-inflammatory cytokines. Conclusion Synovial fluid macrophages may play an important role in the resolution of MSU crystal-induced gouty inflammation by clearing NETs without causing any significant immunological response.

scholarly journals Tempuyung Leaves (Sonchus arvensis) Ameliorates Monosodium Urate Crystal-Induced Gouty Arthritis in Rats through Anti-Inflammatory Effects

2020 ◽  
Vol 8 (A) ◽  
pp. 220-224
Author(s):  
Rachmat Hidayat ◽  
Muhammad Reagan ◽  
Lusia Hayati
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Cytokines ◽  
Gouty Arthritis ◽  
Monosodium Urate ◽  
White Rats ◽  
Tnf Α ◽  
Sonchus Arvensis ◽  
Msu Crystals ◽  
Pro Inflammatory Cytokines

BACKGROUND: Gouty arthritis, a chronic inflammatory disease characterized by severe pain and swelling in one or more synovial joints, as a result from joint deposition of monosodium urate (MSU) crystals. Tempuyung (Sonchus arvensis) is a plant that has been extensively studied in the role of shedding kidney stones and diuretics. It is presumed that it also has great potential in shedding MSU crystals in the joints. AIM: This study focused on exploring the anti-inflammatory role of tempuyung extract (ET) on pro-inflammatory cytokines in gout arthritis white rats. METHODS: The extraction of tempuyung was performed to obtain ET. A total of 30 Wistar rats were randomly divided into the following six groups, each containing five rats: Normal control group, MSU group (negative control), MSU + colchicine group (Col; 0.28 mg/kg), and MSU + ET group (at dose of 25 mg/kg, 50 mg/kg, and 100 mg/kg). Gouty arthritis was induced with 50 ml of MSU solution (20 mg/ml), which was injected into the left ankle joint cavity on day 7. Synovial fluid was evacuated for the examination of Western blotting of tumor necrosis factor-α (TNF-α). A portion of synovial tissue was fixed in 4% paraformaldehyde buffer for histopathological examination. Interleukin (IL)-1β levels in the synovial fluid of the joints were examined by IL-1β rat enzyme-linked immunosorbent assay. Statistical analysis was performed with way ANOVA followed by post hoc. RESULTS: The histopathological image of the MSU model group showed a large number of inflammatory cells depicting an inflammatory reaction. This inflammation response decreased in the ET treatment group in dose-dependent manner. ET showed the effect of decreased pro-inflammatory cytokines expression in both IL-1β and TNF-α, as the dose increased. CONCLUSION: Tempuyung extract possessed an anti-gout arthritis effect in white rats induced by MSU, by reducing the inflammatory response in the synovial joint.

scholarly journals Intrauterine Growth Restriction: Cytokine Profiles of Trophoblast Antigen-Stimulated Maternal Lymphocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Raj Raghupathy ◽  
Majedah Al-Azemi ◽  
Fawaz Azizieh
Keyword(s):  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Intrauterine Growth Restriction ◽  
Mononuclear Cells ◽  
Normal Pregnancy ◽  
Placental Insufficiency ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Anti Inflammatory ◽  
Ifnγ And Tnfα

Intrauterine growth restriction (IUGR) is an important perinatal syndrome that poses several serious short- and long-term effects. We studied cytokine production by maternal peripheral blood lymphocytes stimulated by trophoblast antigens. 36 women with a diagnosis of IUGR and 22 healthy women with normal fetal growth were inducted. Peripheral blood mononuclear cells were stimulated with trophoblast antigens and levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IL-23, IFNγ, and TNFα and the anti-inflammatory cytokines IL-4, IL-10, and IL-13 were measured in culture supernatants by ELISA. IL-8 was produced at higher levels by blood cells of the IUGR group than normal pregnant women, while IL-13 was produced at lower levels. IL-8, IFNγ, and TNFα were higher in IUGR with placental insufficiency than in normal pregnancy. IL-12 levels were higher and IL-10 levels were lower in IUGR with placental insufficiency than in IUGR without placental insufficiency. We suggest that a stronger pro-inflammatory bias exists in IUGR as compared to normal pregnancy and in IUGR with placental insufficiency when compared to IUGR without placental insufficiency. Several ratios of proinflammatory to anti-inflammatory cytokines also support the existence of an inflammatory bias in IUGR.

Pathogenetic molecular mechanisms of chronic rhinosinusitis with nasal polyps associated with asthma

2021 ◽  
Vol 31 (1) ◽  
pp. 7-19
Author(s):  
O. M. Kurbacheva ◽  
M. E. Dyneva ◽  
I. P. Shilovskiy ◽  
E. L. Savlevich ◽  
V. I. Kovchina ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Inflammatory Cytokines ◽  
Nasal Polyps ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Clinical Laboratory ◽  
Compensatory Mechanism ◽  
Local Immunity ◽  
Polyp Tissue ◽  
Anti Inflammatory

The combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype wit1 dysregulation of pro- and anti-inflammatory cytokines as one of t1e leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1st was healthy control (Normal); the 2nd had allergic BA associated with CRSwNP; the 3rd had nonallergic BA associated with CRSwNP; the 4th had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORgt transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dys-regulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.

scholarly journals Hookworm-Derived Metabolites Suppress Pathology in a Mouse Model of Colitis and Inhibit Secretion of Key Inflammatory Cytokines in Primary Human Leukocytes

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Phurpa Wangchuk ◽  
Catherine Shepherd ◽  
Constantin Constantinoiu ◽  
Rachael Y. M. Ryan ◽  
Konstantinos A. Kouremenos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Clinical Signs ◽  
Gas Chromatography Mass Spectrometry ◽  
Trinitrobenzenesulfonic Acid ◽  
Human Leukocytes ◽  
Polar Metabolites ◽  
Anti Inflammatory

ABSTRACT Iatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Using a murine model of trinitrobenzenesulfonic acid-induced colitis and human peripheral blood mononuclear cells, we demonstrated that low-molecular-weight metabolites derived from both somatic extracts (LMWM-SE) and excretory-secretory products (LMWM-ESP) of the hookworm, Ancylostoma caninum, display anti-inflammatory properties. Administration to mice of LMWM-ESP as well as sequentially extracted fractions of LMWM-SE using both methanol (SE-MeOH) and hexane-dichloromethane-acetonitrile (SE-HDA) resulted in significant protection against T cell-mediated immunopathology, clinical signs of colitis, and impaired histological colon architecture. To assess bioactivity in human cells, we stimulated primary human leukocytes with lipopolysaccharide in the presence of hookworm extracts and showed that SE-HDA suppressed ex vivo production of inflammatory cytokines. Gas chromatography-mass spectrometry (MS) and liquid chromatography-MS analyses revealed the presence of 46 polar metabolites, 22 fatty acids, and five short-chain fatty acids (SCFAs) in the LMWM-SE fraction and 29 polar metabolites, 13 fatty acids, and six SCFAs in the LMWM-ESP fraction. Several of these small metabolites, notably the SCFAs, have been previously reported to have anti-inflammatory properties in various disease settings, including IBD. This is the first report showing that hookworms secrete small molecules with both ex vivo and in vivo anti-inflammatory bioactivity, and this warrants further exploration as a novel approach to the development of anti-inflammatory drugs inspired by coevolution of gut-dwelling hookworms with their vertebrate hosts.

scholarly journals MiR-3146 Induces Neutrophil Extracellular Traps to Aggravate Acute Gouty Arthritis

2021 ◽  
Author(s):  
Lizhen Shan ◽  
Di Yang ◽  
Fabo Feng ◽  
Danjie Zhu ◽  
Xiaolin Li
Keyword(s):  
Potential Role ◽  
Gouty Arthritis ◽  
Neutrophil Extracellular Traps ◽  
Sirtuin 1 ◽  
Luciferase Reporter ◽  
Ros Production ◽  
Monosodium Urate ◽  
Acute Gouty Arthritis ◽  
Extracellular Traps ◽  
Msu Crystals

Abstract MiR-3146 plays an important role in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA).The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA). The expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time PCR and western blot. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. AGA model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs. Here, we found miR-3146 expression was dramatically increased in neutrophils of patients with AGA, presenting higher levels of NETs. Monosodium urate (MSU) crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with AGA. MiR-3146-mediated NETs formation may play a potential role in the pathogenesis of AGA.

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.

scholarly journals Induction of Pro- and Anti-Inflammatory Cytokines by Borrelia burgdorferi Lipoproteins in Monocytes Is Mediated by CD14

1999 ◽  
Vol 67 (1) ◽  
pp. 140-147 ◽  
Author(s):  
Guillermo H. Giambartolomei ◽  
Vida A. Dennis ◽  
Barbara L. Lasater ◽  
Mario T. Philipp
Keyword(s):  
Borrelia Burgdorferi ◽  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Human Peripheral Blood ◽  
Peptide Sequence ◽  
Monocytic Cell ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

ABSTRACT We previously showed that heat-killed Borrelia burgdorferi spirochetes and lipidated outer surface protein A (L-OspA) stimulated the in vitro production of interleukin-10 (IL-10) in peripheral blood mononuclear cells (PBMC) from uninfected humans and rhesus monkeys (G. Giambartolomei et al., Infect. Immun. 66:2691–2697, 1998). Here we demonstrate that uninfected human peripheral blood monocytes, but not B or T cells, are the cells that transcribe the IL-10 cytokine gene in response to heat-killed B. burgdorferi. B. burgdorferi similarly induced an upregulation of the IL-1β and IL-6 cytokine genes in monocytes and the production of IL-10 and IL-6 in culture supernatants of the human monocytic cell line THP-1. Purified L-OspA (but not unlipidated OspA [U-OspA] or U-OspC) also stimulated the production of both cytokines in THP-1 cells in a dose-dependent fashion, suggesting that acylation of the OspA protein molecule is required for the production of both anti- and pro-inflammatory cytokines in naive monocytes. A lipohexapeptide that contained the tripalmitoyl-modified cysteine motif (Pam3Cys-Hex) of B. burgdorferi lipoproteins but with an arbitrary peptide sequence had the same effect. Monoclonal antibodies (MAbs) MY4 and 60bca, both of which bind to CD14 and are known to block lipopolysaccharide (LPS)-mediated cytokine production, were able to block L-OspA-mediated IL-10 and IL-6 cytokine production. In contrast, MAb 26ic, which also binds to CD14 but does not block LPS function, failed to inhibit L-OspA-mediated cytokine production. These data suggest that activation of monocytes and production of both anti- and pro-inflammatory cytokines induced by lipoproteins proceeds via the CD14 receptor. LPS binding protein was not required for OspA-induced cytokine production. Our results demonstrate that pro- and anti-inflammatory cytokines induced by B. burgdorferilipoproteins in PBMC are produced by monocytes and that lipoprotein and LPS signaling pathways share at least the initial signaling event that involves the CD14 receptor.

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.

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