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 Citrobacter koseri causing osteomyelitis in a diabetic foot with concomitant acute gouty arthritis successfully treated with ertapenem

2019 ◽  
Vol 12 (7) ◽  
pp. e230432
Author(s):  
Dillon Tinevez ◽  
Nebojsa Nick Knezevic
Keyword(s):  
Septic Arthritis ◽  
Gouty Arthritis ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Acute Gouty Arthritis ◽  
Monosodium Urate Crystals ◽  
X Ray ◽  
Fluid Analysis ◽  
Wound Culture ◽  
Urate Crystals

We present an elderly diabetic man with left hallux pain and drainage who was initially diagnosed with acute gouty arthritis using the diagnostic rule for acute gout and monosodium urate crystals presented on synovial fluid analysis. Further investigation with surgical debridement, plain X-ray, MRI and wound culture revealed concomitant Citrobacter koseri septic arthritis with osteomyelitis. C. koseri is considered an opportunistic infection that rarely causes musculoskeletal infections. Acute gouty arthritis and septic arthritis are rarely seen occurring concomitantly in the same joint and are often difficult to differentiate due to similar findings on exam and imaging. The present case illustrates that osteomyelitis with an opportunistic organism can present concomitantly with acute gouty arthritis, and the diagnosis of one should not exclude the other.

scholarly journals Hyperuricemia and Gout – Ins and Out

2020 ◽  
Vol 15 (2) ◽  
pp. 227-234
Author(s):  
Md Abdur Razzak ◽  
Quazi Audry Arafat Rahman ◽  
Fahtiha Nasreen
Keyword(s):  
Gouty Arthritis ◽  
Polarized Light ◽  
Acute Gout ◽  
Women Patients ◽  
Monosodium Urate ◽  
Tophaceous Gout ◽  
First Metatarsal ◽  
Birefringent Crystals ◽  
Inflammatory Drugs ◽  
Urate Crystals

Gout is a condition characterized by the deposition of monosodium urate crystals in the joints or soft tissue. The four phases of gout include asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout and chronic tophaceous gout. The peak incidence occurs in patients 30 to 50 years old, and the condition is much more common in men than in women. Patients with asymptomatic hyperuricemia do not require treatment, but efforts should be made to lower their urate levels by encouraging them to make changes in diet or lifestyle. Acute gout most commonly affects the first metatarsal joint of the foot, but other joints are also commonly involved. Definitive diagnosis requires joint aspiration with demonstration of birefringent crystals in the synovial fluid under a polarized light microscope. Treatment includes nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroids and analgesics. In patients without complications, NSAID therapy is preferred. JAFMC Bangladesh. Vol 15, No 2 (December) 2019: 227-234

Treatment of acute gout

2016 ◽  
Author(s):  
Puja Khanna
Keyword(s):  
Inflammatory Arthritis ◽  
Adult Population ◽  
Gouty Arthritis ◽  
Acute Gout ◽  
Monosodium Urate ◽  
Epidemiological Evidence ◽  
Acute Gouty Arthritis ◽  
Over Time ◽  
Underlying Inflammation ◽  
Urate Crystals

Acute gout is a common inflammatory arthritis in the adult population. Epidemiological evidence suggests that the prevalence of gout is steadily on the rise due to longevity, coexisting comorbidities, and iatrogenic causes contributing to hyperuricaemia. Acute gout usually presents as a self-limiting flare of synovitis that occurs due to deposition of monosodium urate crystals. The frequency of flares generally increases over time in patients who continue to have hyperuricaemia and their risk factors for acute gout attacks have not been adequately addressed. Effective treatment of acute gouty arthritis is primary focused on pain which is the primary symptom but must target both the pain and underlying inflammation. Acute gout is frequently treated with non-steroidal anti-inflammatory agents, colchicine, and corticosteroids. This chapter reviews the available therapies for management of acute gout and ones that have shown promising results.

scholarly journals Tu-Teng-Cao Extract Alleviates Monosodium Urate-Induced Acute Gouty Arthritis in Rats by Inhibiting Uric Acid and Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rongmei Yao ◽  
Zihan Geng ◽  
Xin Mao ◽  
Yanyan Bao ◽  
Shanshan Guo ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gouty Arthritis ◽  
Histological Evaluation ◽  
Therapeutic Effects ◽  
Monosodium Urate ◽  
Cell Degeneration ◽  
Acute Gouty Arthritis ◽  
Monosodium Urate Crystals ◽  
Potassium Oxonate ◽  
Urate Crystals

Gouty arthritis is an inflammatory joint disease closely related to hyperuricemia. It is characterized by deposition of monosodium urate crystals in the joints, resulting in an intense inflammatory process and pain. Control of hyperuricemia and anti-inflammation treatments are the main therapeutic approaches. However, the commonly used drugs for inhibiting uric acid and acute gouty arthritis have obvious gastrointestinal and renal toxicity; thus, there is an urgency to develop new alternative therapeutic drugs. An extract of Tu-Teng-Cao (TTC), a compound drug used in traditional Chinese medicine, has been widely applied to the clinical treatment of arthritis. In this study, we investigated the therapeutic effects of TTC on gouty arthritis. In this study, an animal model of acute gouty arthritis with hyperuricemia was established using potassium oxonate and monosodium urate crystals. After treatment with TTC, the results showed obvious therapeutic effects on the rat model of acute gouty arthritis. The treatment significantly attenuated the degree of ankle swelling, inflammation, and dysfunction index, and the levels of proinflammatory cytokines. In addition, TTC has significant antihyperuricemia activity in rats with hyperuricemia induced by potassium oxonate. Histological evaluation showed that TTC relieved pathological damage in rats with acute gouty arthritis induced by monosodium urate crystals. All the groups treated with TTC showed improvement in cartilage degeneration, cell degeneration, synovial hyperplasia, and inflammatory cell invasion in the ankle joint of rats. TTC significantly alleviated swelling, inflammation, and bleeding of the renal corpuscle and convoluted tubules of rats. The results of this study suggest that TTC is capable of treating gouty arthritis and decreasing ankle injury through the control of uric acid and inflammation.

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 Ameliorative Effects of Cardamonin on Monosodium Urate-Induced Gouty Arthritis through Inhibiting NLRP3 Inflammasome Mediation

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 898
Author(s):  
Chih-Chien Wang ◽  
Jeng-Wei Lu ◽  
Yi-Jen Peng ◽  
Chian-Her Lee ◽  
Herng-Sheng Lee ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Gouty Arthritis ◽  
Inflammasome Activation ◽  
Monosodium Urate ◽  
In Vivo Models ◽  
Macrophage Cells ◽  
Caspase 1 ◽  
Cox 2

Background and Objectives: Gouty arthritis is an acute inflammatory response caused by the precipitation of monosodium urate (MSU) crystals in joints. The triggering of MSU leads to increased production of inflammatory cytokines, such as interleukin-1β, which in turn lead to the formation of macromolecular complexes, referred to as inflammasomes. Thorough characterization of the NLRP3 inflammasome can be used as an indicator of an immune response against harmful stimuli. Cardamonin is a chalcone, mainly found in the seeds of Alpinia katsumadai, and exhibits anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines in vitro. However, the mechanism by which cardamonin treatment alleviates gouty arthritis has yet to be fully elucidated. Materials and Methods: In vitro or in vivo models were used to study whether cardamonimn inhibited NLRP3 inflammasome activation or suppressed gouty inflammation. Results: In the current study, we determined that most NLRP3 was released passively after MSU stimulation, and this release of NLRP3 promoted caspase-1 activation and IL-1β secretion. Cardamonin was shown to decrease both the activity of caspase-1 and secretion of IL-1β in J774A.1 macrophage cells subjected to MSU stimulation. Cardamonin was also shown to attenuate the production of COX-2 in MSU-stimulated J774A.1 macrophage cells. Finally, cardamonin reduced the thickness of the synovial lining and the infiltration of gouty arthritis in a rat model. Conclusions: Overall, cardamonin significantly attenuated IL-1β secretion, caspase-1 activity, and COX-2 production stimulated by MSU. These findings provide new insights into the molecular mechanisms underlying the effects of cardamonin treatment for gouty arthritis.

scholarly journals Could MicroRNAs be Regulators of Gout Pathogenesis?

2015 ◽  
Vol 36 (6) ◽  
pp. 2085-2092 ◽  
Author(s):  
Yangang Wang ◽  
Donghua Xu ◽  
Bin Wang ◽  
Xu Hou
Keyword(s):  
Inflammatory Arthritis ◽  
Inflammatory Diseases ◽  
Gouty Arthritis ◽  
Noncoding Rnas ◽  
Monosodium Urate ◽  
Regulate Gene Expression ◽  
Acute Gouty Arthritis ◽  
Monosodium Urate Crystals ◽  
Urate Crystals

MicroRNAs (miRNAs) are a class of noncoding RNAs that mainly negatively regulate gene expression. miRNAs have important roles in many diseases, including inflammatory diseases. Gout is a common arthritis caused by deposition of monosodium urate crystals within joints. Recent studies suggested that miRNAs may be involved in the development of inflammatory arthritis, including acute gouty arthritis. In the present review, we systemically discuss relevant publications in order to provide a better understanding on the possible role of miRNAs in gout. miRNAs may act as regulators of gout pathogenesis via several pathways. Targeting miRNAs may be a promisingstrategy in the treatment of gout.

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