scholarly journals Natural ACTH Relieves Acute Inflammation of Gout by Changing the Function of Macrophages

2021 ◽  
Author(s):  
Rui Xu ◽  
Li Zhao ◽  
Jiyu Liu ◽  
Lin Cao ◽  
Tianyi Zhao ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Joint Inflammation ◽  
Transcriptional Level ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Functional Changes ◽  
Pain Scores ◽  
Urate Crystals

Abstract Objective: Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU) -induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. This study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. Methods: We analysed the variations in VAS pain scores of five patients, knowing the time of action, and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in mouse model was evaluated by studies in vivo. In vitro studies we evaluated the effect of natural ACTH on macrophage and revealed different functions of ACTH and dexamethasone on macrophage in the transcriptional level. Results: In patients with acute gout, natural ACTH can quickly alleviate pain and has no effect on the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exert different effects on the transcription of some related genes.Conclusion: Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone in the transcriptional level.

scholarly journals Natural ACTH Relieves Acute Inflammation of Gout by Changing the Function of Macrophages

2021 ◽  
Author(s):  
Rui Xu ◽  
Li Zhao ◽  
Jiyu Liu ◽  
Lin Cao ◽  
Tianyi Zhao ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Joint Inflammation ◽  
Transcriptional Level ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Functional Changes ◽  
Pain Scores ◽  
Urate Crystals

Abstract Objective: Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU) -induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. This study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. Methods: We analysed the variations in VAS pain scores of five patients, knowing the time of action, and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in mouse model was evaluated by studies in vivo. In vitro studies we evaluated the effect of natural ACTH on macrophage and revealed different functions of ACTH and dexamethasone on macrophage in the transcriptional level. Results: In patients with acute gout, natural ACTH can quickly alleviate pain and has no effect on the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exert different effects on the transcription of some related genes.Conclusion: Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone in the transcriptional level.

scholarly journals NLRP3- and AIM2-autonomy in a mouse model of MSU crystal-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1[beta] expression as relevant therapy for gout patients.

2019 ◽  
Author(s):  
Alexandre Mariotte ◽  
Aurore Decauwer ◽  
Chrystelle Po ◽  
Cherine Abou-Faycal ◽  
Angelique Pichot ◽  
...  
Keyword(s):  
Mouse Model ◽  
Acute Inflammation ◽  
Joint Inflammation ◽  
Inflammatory Action ◽  
Recognition Receptor ◽  
Msu Crystals

The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1b in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1b; secretion in vitro, the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. Here, we provide an extensive clinical, biological and molecular characterization of the acute uratic inflammation mouse model induced by subcutaneous injection of MSU crystals, which accurately mimics human gout. Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities, among which the use of topical application of imiquimod to promote interferon-dependent anti-inflammatory action maybe relevant.

scholarly journals Huzhang Tongfeng Granule Improves Monosodium Urate-Induced Inflammation of Gouty Arthritis Rat Model by Downregulation of Cyr61 and Related Cytokines

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Mi Zhou ◽  
Kan Ze ◽  
Yifei Wang ◽  
Xin Li ◽  
Liang Hua ◽  
...  
Keyword(s):  
Pharmaceutical Preparation ◽  
Gouty Arthritis ◽  
Inflammatory Factors ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Rat Models ◽  
Hematoxylin And Eosin ◽  
Fibroblast Like Synoviocytes

Objective. Gouty arthritis (GA) is a noninfectious inflammatory disease characterized by self-limited and severe pain. Huzhang Tongfeng granule is one of the most effective traditional Chinese medicines in the treatment of acute GA. However, its effects on the inflammatory factors in the process of acute gout inflammation remain unknown. In the present study, we aimed to evaluate the effect of Huzhang Tongfeng granule on the expressions of Cyr61 and related inflammatory factors in both experimental gout models in vivo and in vitro. Methods. Huzhang Tongfeng granule was provided by the pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. The expressions of Cyr61, IL-1β, TNF-α, and IL-6 in monosodium urate- (MSU-) induced rat models and fibroblast-like synoviocytes (FLSs) were determined by RT-PCR, Western blotting analysis, ELISA, immunohistochemistry, and hematoxylin and eosin staining. Results. Huzhang Tongfeng granule could downregulate the expressions of IL-1β, TNF-α, and IL-6 to some extent by inhibiting the expression of Cyr61. Conclusions. Collectively, our findings indicated that Cyr61 was highly expressed in rat models of gout. By inhibiting the expression of Cyr61, Huzhang Tongfeng granule could partially attenuate the inflammation induced by MSU crystal.

scholarly journals Cyr61 Promotes Inflammation of a Gouty Arthritis Model in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Mi Zhou ◽  
Kan Ze ◽  
Liang Hua ◽  
Liu Liu ◽  
Le Kuai ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Acute Inflammation ◽  
Gouty Arthritis ◽  
Dependent Manner ◽  
Monosodium Urate ◽  
Synovial Tissues

Background. Cyr61 is considered a novel proinflammatory factor. Gouty arthritis (GA) is a self-limited inflammatory reaction caused by monosodium urate (MSU) crystals. In this study, we assessed the role of Cyr61 in the inflammatory process of GA. Methods. We investigated the expression of Cyr61 in MSU-induced rat gout models and MSU-stimulated rat fibroblast-like synovial (FLS) cells. After inhibiting the expression of Cyr61, levels of IL-1β, TNF-α, and IL-6 were detected by ELISA, qPCR, western blot, and immunohistochemical methods. We probed the downstream NF-κB signaling pathway using the NF-κB inhibitor PDTC, and levels of NF-κB and p-NF-κB were detected by western blot and qPCR. Results. Our results demonstrate that Cyr61 plays a potent role in the formation of local inflammation in vitro and in vivo. Cyr61 was highly expressed in synovial tissues of gout models, and the expression of Cyr61 protein was also significantly increased in MSU-stimulated FLS cells. Cyr61 promoted MSU-induced acute inflammation via the NF-κB signaling pathway. Conclusions. Our study has revealed that Cyr61 is an important regulatory factor for the initiation of inflammation in GA. The high expression of Cyr61 protein can induce synovial cells to produce many inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, partly in an NF-κB-dependent manner. Thus, inhibition of Cyr61 could be a new target and strategy for the prevention and treatment of GA.

Dolichos falcata Klein attenuated the inflammation induced by monosodium urate crystals in vivo and in vitro

2013 ◽  
Vol 150 (2) ◽  
pp. 545-552 ◽  
Author(s):  
Lvyi Chen ◽  
Mahmutjian Mola ◽  
Xukun Deng ◽  
Zhinan Mei ◽  
Xianju Huang ◽  
...  
Keyword(s):  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Urate Crystals

scholarly journals Neutrophil microvesicles resolve gout by inhibiting C5a-mediated priming of the inflammasome

2015 ◽  
Vol 75 (6) ◽  
pp. 1236-1245 ◽  
Author(s):  
Arun Cumpelik ◽  
Barbara Ankli ◽  
Daniel Zecher ◽  
Jürg A Schifferli
Keyword(s):  
Acute Inflammation ◽  
Gouty Arthritis ◽  
Surface Expression ◽  
Joint Disease ◽  
Inflammasome Activation ◽  
Acute Gout ◽  
Mediated Priming

ObjectivesGout is a highly inflammatory but self-limiting joint disease induced by the precipitation of monosodium urate (MSU) crystals. While it is well established that inflammasome activation by MSU mediates acute inflammation, little is known about the mechanism controlling its spontaneous resolution. The aim of this study was to analyse the role of neutrophil-derived microvesicles (PMN-Ecto) in the resolution of acute gout.MethodsPMN-Ecto were studied in a murine model of MSU-induced peritonitis using C57BL/6, MerTK−/−and C5aR−/−mice. The peritoneal compartment was assessed for the number of infiltrating neutrophils (PMN), neutrophil microvesicles (PMN-Ecto), cytokines (interleukin-1β, TGFβ) and complement factors (C5a). Human PMN-Ecto were isolated from exudates of patients undergoing an acute gouty attack and functionally tested in vitro.ResultsC5a generated after the injection of MSU primed the inflammasome for IL-1β release. Neutrophils infiltrating the peritoneum in response to C5a released phosphatidylserine (PS)-positive PMN-Ecto early on in the course of inflammation. These PMN-Ecto in turn suppressed C5a priming of the inflammasome and consequently inhibited IL-1β release and neutrophil influx. PMN-Ecto-mediated suppression required surface expression of the PS-receptor MerTK and could be reproduced using PS-expressing liposomes. In addition, ectosomes triggered the release of TGFβ independent of MerTK. TGFβ, however, was not sufficient to control acute MSU-driven inflammation in vivo. Finally, PMN-Ecto from joint aspirates of patients with gouty arthritis had similar anti-inflammatory properties.ConclusionsPMN-Ecto-mediated control of inflammasome-driven inflammation is a compelling concept of autoregulation initiated early on during PMN activation in gout.

scholarly journals Monosodium Urate Crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response

2021 ◽  
Author(s):  
Isidoro Cobo ◽  
Anyan Cheng ◽  
Jessica Saich ◽  
Roxana Coras ◽  
Alyssa Torres ◽  
...  
Keyword(s):  
Target Genes ◽  
Gouty Arthritis ◽  
Inflammasome Activation ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Monosodium Urate Crystals ◽  
Slc Transporters ◽  
Biochemical Assays ◽  
Urate Crystals

How macrophages are programmed to respond to monosodium urate crystals (MSUc) is incompletely understood partly due to the use of a toll-like receptor-induced priming step. Here, using genome wide transcriptomic analysis and biochemical assays we demonstrate that MSUc alone induces an in vitro metabolic and inflammatory transcriptional program in both human and murine macrophages markedly distinct from that induced by LPS. Genes uniquely up-regulated in response to MSUc belonged to lipids, glycolysis, and transport of small molecules via SLC transporters pathways. Sera from individuals and mice with acute gouty arthritis provided further evidence for this metabolic rewiring. This distinct macrophage activation may explain the initiating mechanisms in acute gout flares and is regulated through JUN binding to the promoter of target genes through activation of JNK (but not by P38) in a process that is independent of inflammasome activation. Finally, pharmacological JNK inhibition limited MSUc-induced inflammation in animal models of acute gouty inflammation.

scholarly journals Aberrantly high activation of a FoxM1–STMN1 axis contributes to progression and tumorigenesis in FoxM1-driven cancers

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Liu ◽  
Jipeng Li ◽  
Ke Wang ◽  
Haiming Liu ◽  
Jianyong Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Soft Agar ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Strong Positive Correlation ◽  
Cell Viability Assay ◽  
High Level

AbstractFork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

scholarly journals Phosphorylation of Serine 303 Is a Prerequisite for the Stress-Inducible SUMO Modification of Heat Shock Factor 1

2003 ◽  
Vol 23 (8) ◽  
pp. 2953-2968 ◽  
Author(s):  
Ville Hietakangas ◽  
Johanna K. Ahlskog ◽  
Annika M. Jakobsson ◽  
Maria Hellesuo ◽  
Niko M. Sahlberg ◽  
...  
Keyword(s):  
Heat Shock ◽  
Phosphorylation Site ◽  
Stress Granules ◽  
Heat Shock Factor ◽  
Transcriptional Level ◽  
Heat Shock Factor 1 ◽  
Protection Mechanism ◽  
Sumo Modification

ABSTRACT The heat shock response, which is accompanied by a rapid and robust upregulation of heat shock proteins (Hsps), is a highly conserved protection mechanism against protein-damaging stress. Hsp induction is mainly regulated at transcriptional level by stress-inducible heat shock factor 1 (HSF1). Upon activation, HSF1 trimerizes, binds to DNA, concentrates in the nuclear stress granules, and undergoes a marked multisite phosphorylation, which correlates with its transcriptional activity. In this study, we show that HSF1 is modified by SUMO-1 and SUMO-2 in a stress-inducible manner. Sumoylation is rapidly and transiently enhanced on lysine 298, located in the regulatory domain of HSF1, adjacent to several critical phosphorylation sites. Sumoylation analyses of HSF1 phosphorylation site mutants reveal that specifically the phosphorylation-deficient S303 mutant remains devoid of SUMO modification in vivo and the mutant mimicking phosphorylation of S303 promotes HSF1 sumoylation in vitro, indicating that S303 phosphorylation is required for K298 sumoylation. This finding is further supported by phosphopeptide mapping and analysis with S303/7 phosphospecific antibodies, which demonstrate that serine 303 is a target for strong heat-inducible phosphorylation, corresponding to the inducible HSF1 sumoylation. A transient phosphorylation-dependent colocalization of HSF1 and SUMO-1 in nuclear stress granules provides evidence for a strictly regulated subnuclear interplay between HSF1 and SUMO.

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