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 NFIL3 Facilitates Neutrophil Autophagy, Neutrophil Extracellular Trap Formation and Inflammation During Gout via REDD1-Dependent mTOR Inactivation

2021 ◽  
Vol 8 ◽  
Author(s):  
Honghu Tang ◽  
Chunyu Tan ◽  
Xue Cao ◽  
Yi Liu ◽  
Hua Zhao ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Expression Patterns ◽  
Gouty Arthritis ◽  
Mtor Pathway ◽  
Neutrophil Extracellular Trap ◽  
Inflammatory Factors ◽  
Loss Of Function ◽  
Blood Neutrophils

Autophagy pathways play an important role in immunity and inflammation via pathogen clearance mechanisms mediated by immune cells, such as macrophages and neutrophils. In particular, autophagic activity is essential for the release of neutrophil extracellular traps (NETs), a distinct form of active neutrophil death. The current study set out to elucidate the mechanism of the NFIL3/REDD1/mTOR axis in neutrophil autophagy and NET formation during gout inflammation. Firstly, NFIL3 expression patterns were determined in the peripheral blood neutrophils of gout patients and monosodium urate (MSU)-treated neutrophils. Interactions between NFIL3 and REDD1 were identified. In addition, gain- or loss-of-function approaches were used to manipulate NFIL3 and REDD1 in both MSU-induced neutrophils and mice. The mechanism of NFIL3 in inflammation during gout was evaluated both in vivo and in vitro via measurement of cell autophagy, NET formation, MPO activity as well as levels of inflammatory factors. NFIL3 was highly-expressed in both peripheral blood neutrophils from gout patients and MSU-treated neutrophils. NFIL3 promoted the transcription of REDD1 by binding to its promoter. REDD1 augmented neutrophil autophagy and NET formation by inhibiting the mTOR pathway. In vivo experimental results further confirmed that silencing of NFIL3 reduced the inflammatory injury of acute gouty arthritis mice by inhibiting the neutrophil autophagy and NET formation, which was associated with down-regulation of REDD1 and activation of the mTOR pathway. Taken together, NFIL3 can aggravate the inflammatory reaction of gout by stimulating neutrophil autophagy and NET formation via REDD1/mTOR, highlighting NFIL3 as a potential therapeutic target for gout.

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 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.

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 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 In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
High Mobility ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

scholarly journals The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Qing Lv ◽  
Qinghua Xia ◽  
Anshu Li ◽  
Zhiyong Wang
Keyword(s):  
Tumor Microenvironment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Stomach Carcinoma ◽  
Downstream Target ◽  
Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

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