Arthritis Research Articles

P2X7R Mediates the Synergistic Effect of ATP and MSU Crystals to Induce Acute Gouty Arthritis.

Activation of the nod-like receptor protein 3 (NLRP3) inflammasome by monosodium urate (MSU) crystals has been identified as the molecular basis for the acute inflammatory response in gouty arthritis. However, MSU crystals alone are not sufficient to induce acute gouty arthritis (AGA). Adenosine triphosphate (ATP) is an endogenous signaling molecule involved in the NLRP3 inflammasome activation. We aimed to explore the role of ATP in MSU crystal-induced AGA development. In peripheral blood mononuclear cell-derived macrophages obtained from gout patients, we observed a synergistic effect of ATP on MSU crystal-induced IL-1β release. Furthermore, in a rat model of spontaneous gout, we demonstrated that a synergistic effect of ATP and MSU crystals, but not MSU crystals alone, is essential for triggering AGA. Mechanistically, this synergistic effect is achieved through the purinergic receptor P2X7 (P2X7R). Blockade of P2X7R prevented AGA induction in rats after local injection of MSU crystals, and carrying the mutant hP2X7R gene contributed to the inhibition of NLRP3 inflammasome activation induced by costimulation of MSU crystals and ATP in vitro. Taken together, these results support the synergistic effect of ATP on MSU crystal-induced NLRP3 inflammasome activation facilitating inflammatory episodes in AGA. In this process, P2X7R plays a key regulatory role, suggesting targeting P2X7R to be an attractive therapeutic strategy for the treatment of AGA.

RNA sequencing analysis reveals the potential therapeutic mechanisms of Huzhang Tongfeng granule in MSU-induced acute gouty arthritis mouse model

BackgroundGout is one of the most prevailing inflammatory arthritis, in which joint pain and dysfunction may drastically reduce patients' quality of life, work efficiency, and increase the burden of medical treatment. The Huzhang Tongfeng granule (HZTFG) has been utilized clinically for more than 30 years with satisfactory effects and no significant adverse reactions. However, the mechanisms that underlie HZTFG's effect remain indeterminate. MethodsFirstly, the Liquid Chromatography-Mass Spectrometry (LC-MS) analyses were applied to clarify the multi-components of HZTFG to establish the quality control parameters. After the monosodium urate (MSU) crystals induced Acute gouty arthritis (AGA) model was established, behavioral testing, joint swelling, hematoxylin, and eosin (H&E) staining were applied to assess the effect of HZTFG on improving joint pain, swelling, synovial inflammation of the MSU crystals-injected mice. Moreover, to further understand the underlying mechanism of the action of HZTFG on AGA, RNA Sequencing (RNA-seq) analysis was performed to detect differentially expressed genes (DEGs) after HZTFG treatment. Thereafter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched via gene set enrichment analysis (GSEA) to assess the functions and pathways of DEGs. Furthermore, Reverse Transcription Polymerase Chain Reaction (RT-qPCR) analysis and enzyme-linked immunosorbent assay (ELISA) were applied for validation in vivo. ResultsAfter treatment with HZTFG, RNA-seq results revealed 44 DEGs, of which 20 genes were remarkably down-regulated and 24 genes were up-regulated. Besides, the expression of these assayed genes were noticeably decreased, including Cxcl1, Cxcl2, Cebpb, Lcn2, Ptgs2, Mmp13, Fos, Socs3, Sele, and Junb. Moreover, animal experiments also demonstrated that TNF signaling pathway and IL-17 signaling pathway are key pathways in HZTFG treated MSU-induced AGA mouse model. ConclusionHZTFG attenuated MSU crystals-induced inflammatory response through TNF and IL-17 signaling pathways by inhibiting the activation of related chemokines, inflammatory proteins, transcription factors, suppressor of cytokine signaling, and adhesion molecule in AGA. This study further provides the potential therapeutic targets for AGA treatment.

Mast Cell-Associated Serotonin in Acupoint Contributes to Acupuncture Analgesia in Arthritis Rats by Mediating ATP Release.

The activation of subcutaneous mast cells (MCs) helps to trigger the analgesic effect induced by acupuncture (AP), a traditional oriental therapy, that has been gradually accepted worldwide. This work aimed to reveal whether the serotonin (5-hydroxytryptamine, 5-HT) released from MCs plays an important role in this process, which has a controversial effect in the mechanism of pain. In vivo tests, a 20-min session of AP was applied at Zusanli acupuncture point (acupoint) of acute ankle arthritis rats. Pain thresholds of the injured hindpaw were assessed to reflect the pain state, and the targeting substances in the interstitial space of the treated acupoint were sampled by microdialysis. In vitro experiments, exogenous 5-HT (exo-5-HT) was introduced to mediate adenosine triphosphate (ATP) release from cultured MCs. Needling promoted 5-HT accumulation at the Zusanli acupoint, which was prevented by sodium cromolyn. AP's analgesic effect was suppressed by the inhibition of 5-HT receptors at the acupoint, especially 5-HT1A subtype. In vitro tests, mechanical perturbation mimicking needling stimulation induced MCs to release 5-HT. 1 μM and 10 μM of exo-5-HT facilitated ATP release, which was restrained by blocking of 5-HT1 receptors rather than 5-HT3 receptors. As 5-HT, ATP and adenosine were also transiently accumulated in the treated acupoint during needling. Promoting ATP hydrolysis or activation adenosine A1 receptors duplicated AP analgesic effect. Finally, the inhibition of ATP receptors by suramin or pyridoxal phosphate-6-azo tetrasodium salt hydrate (PPADS) prevented AP analgesic effect. Our results suggest that MC-associated 5-HT release at acupoints contributes to AP analgesia, and the mediation of ATP secretion through 5-HT1A receptors might be the underlying mechanism at play. ATP could facilitate adenosine production or the propagation of needling signals.

The Presence of Hip Joint Effusion on MRI Is Predictive of a Grade 4 Femoral Neck Stress Injury.

One of the most debilitating types of bone stress injuries is those occurring at the femoral neck. This problem occurs in the military population with much higher incidence than in the normal population and is of great concern to military medical providers. Early detection and accurate diagnosis are key in protecting soldiers and recruits from sustaining a potentially career-ending fracture. In a case study, a 16-year-old elite male distance runner presented with hip pain. MRI found hip joint effusion but was unremarkable for marrow edema and a low-signal fracture line. The initial diagnosis was acute arthritis; however, a follow-up radiograph 1 month later, after the patient had been refraining from running, confirmed a significant non-displaced compression-side Grade 4 femoral neck stress injury (FNSI). In light of the case study and our similar clinical experience, we tested the hypothesis that an MRI study positive for an FNSI, combined with the evidence of a hip joint effusion, is indicative of a Grade 4 FNSI, even without visualization of a low-signal intensity fracture line on T1 or short tau inversion recovery images. Recruits in Army Basic Combat Training were included in the investigation if 1) diagnosed with a unilateral FNSI, 2) had an initial positive MRI for an FNSI, 3) had a positive bone scan for uptake in the femoral neck area (to validate the diagnosis), 4) had no other hip/pelvis injuries, and 5) had a follow-up MRI within 60 days. Hip joint effusion was defined as 1) ≥2-mm measurable difference in the thickness of fluid along the length of the involved femoral neck when compared to the contralateral uninvolved femoral neck on the initial MRI; 2) visibly assessed as a prominent collection of fluid distending the posterior hip joint capsule on the initial MRI coronal short tau inversion recovery sequence (called the "flash sign"). A total of 162 recruits met the study inclusion criteria. For the detection of a Grade 4 FNSI on the first MRI, the sensitivity, specificity, and positive predictive value of the measured joint effusion criteria were 0.52, 0.94, and 0.89, respectively. or the non-measured flash sign, these values were 0.70, 0.83, and 0.80, respectively. Both the measured hip joint effusion criteria and the non-measured flash sign were predictive of a Grade 4 FNSI and may be useful in clinical evaluation.

Anti-Inflammatory Effects of Polyphenols from Plum (Prunus salicina Lindl) on RAW264.7 Macrophages Induced by Monosodium Urate and Potential Mechanisms.

Acute gouty arthritis is an acute inflammatory reaction caused by the deposition of monosodium urate (MSU) crystals in joints and surrounding soft tissues. Controlling inflammation is the key to preventing acute gouty arthritis. Anti-inflammatory activities and the possible molecular mechanisms of plum (Prunus salicina Lindl cv. "furong") polyphenols (PSLP) on RAW264.7 macrophage cells induced by monosodium urate were investigated. PPSF significantly inhibited the activity of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18). In addition, PPSF exhibited excellent activation of superoxide dismutase (SOD) activity and reduction of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels in RAW264.7 macrophages. The results of global screening of all transcripts by RNA-seq revealed 8585 differentially expressed genes between the PSLP-treated group and the MUS group. From GO analysis, PSLP could affect the occurrence and development of RAW264.7 macrophage inflammation through biological processes, such as organic substance metabolism, intracellular organelles, and binding function. The regulation mechanism of PSLP on MSU-induced RAW264.7 macrophage inflammation may be achieved through the HIF-1 signaling pathway, renal cell carcinoma, the ErbB signaling pathway, and the FoxO signaling pathway. Therefore, PSLP has great prospects in the prevention of gout and similar inflammatory diseases.

Spinal pain processing in arthritis: Neuron and glia (inter)actions.

Diseases of joints are among the most frequent causes of chronic pain. In the course of joint diseases, the peripheral and the central nociceptive system develop persistent hyperexcitability (peripheral and central sensitization). This review addresses the mechanisms of spinal sensitization evoked by arthritis. Electrophysiological recordings in anesthetized rats from spinal cord neurons with knee input in a model of acute arthritis showed that acute spinal sensitization is dependent on spinal glutamate receptors (AMPA, NMDA, and metabotropic glutamate receptors) and supported by spinal actions of neuropeptides such as neurokinins and CGRP, by prostaglandins, and by proinflammatory cytokines. In several chronic arthritis models (including immune-mediated arthritis and osteoarthritis) spinal glia activation was observed to be coincident with behavioral mechanical hyperalgesia which was attenuated or prevented by intrathecal application of minocycline, fluorocitrate, and pentoxyfylline. Some studies identified specific pathways of micro- and astroglia activation such as the purinoceptor- (P2 X7 -) cathepsin S/CX3 CR1 pathway, the mobility group box-1 protein (HMGB1), and toll-like receptor 4 (TLR4) activation, spinal NFκB/p65 activation and others. The spinal cytokines TNF, interleukin-6, interleukin-1β, and others form a functional spinal network characterized by an interaction between neurons and glia cells which is required for spinal sensitization. Neutralization of spinal cytokines by intrathecal interventions attenuates mechanical hyperalgesia. This effect may in part result from local suppression of spinal sensitization and in part from efferent effects which attenuate the inflammatory process in the joint. In summary, arthritis evokes significant spinal hyperexcitability which is likely to contribute to the phenotype of arthritis pain in patients.

Pro-Inflammatory of PRDM1/SIRT2/NLRP3 Axis in Monosodium Urate-Induced Acute Gouty Arthritis

PR domain-containing 1 with zinc finger domain (PRDM1) has been reported as a promoter of inflammation, which is a critical process involved in the pathogenesis of acute gouty arthritis. Herein, we sought to ascertain the function of PRDM1 in the development of acute gouty arthritis and related mechanisms. At first, peripheral blood-derived monocytes from patients with acute gouty arthritis and healthy individuals were collected as experimental samples. Then, macrophages were induced from monocytes using phorbol myristate acetate (PMA). The expression patterns of PRDM1, sirtuin 2 (SIRT2), and NLR family, pyrin domain-containing 3 (NLRP3) were characterized by RT-qPCR and Western blot assay. PMA-induced macrophages were stimulated by monosodium urate (MSU) for in vitro experimentation. Meanwhile, a murine model of MSU-induced acute gouty arthritis was established for in vivo validation. PRDM1 was highly expressed while SIRT2 poorly expressed in patients with acute gouty arthritis. Loss of PRDM1 could reduce NLRP3 inflammasome and mature IL-1β levels and downregulate inflammatory cytokines in macrophages, which contributed to protection against acute gouty arthritis. Furthermore, results showed that PRDM1 could inhibit SIRT2 expression via binding to the deacetylase SIRT2 promoter. Finally, the in vivo experiments demonstrated that PRDM1 increased NLRP3 inflammasome and mature IL-1β through transcriptional inhibition of SIRT2, whereby aggravating MSU-induced acute gouty arthritis. To sum up, PRDM1 increased NLRP3 inflammasome through inhibiting SIRT2, consequently aggravating MSU-induced acute gouty arthritis.

Associations of serum leptin levels with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice.

The roles of serum leptin in knee joint inflammation are unclear. The objective of this study was to identify any associations of serum leptin level with intra-articular inflammatory cytokine levels in acute arthritic and nonarthritic knees of mice. Acute arthritis was induced by intra-articular injection of 2% carrageenan. Three groups (leptin-deficient ob/ob, wild-type (WT) and high-fat diet (HFD)-fed WT) were made. Serum leptin and inflammatory cytokines in the infrapatellar fat pad and synovium were measured before and 24 hr after injection. Affected knee joints were excised for histology 24 hr after injection. The HFD-WT group had significantly higher serum leptin than the ob/ob and WT groups before and after carrageenan injection. The HFD-WT group had significantly higher IL-1? and IL-6 in the infrapatellar fat pad and synovium than ob/ob and WT before injection but significantly lower IL-1?, IL-6 and TNF-? than the ob/ob group at 24 hr. Hyperleptinemia induced by a HFD is involved in low-grade intra-articular inflammation in nonarthritic knee joints. In contrast, leptin deficiency causes excessive intra-articular inflammation in carrageenan-induced acute arthritis. Leptin alleviates acute arthritis, while chronic hyperleptinemia is involved in low-grade inflammation in normal knee joints. J. Med. Invest. 70 : 54-59, February, 2023.

HQL6 serves as a novel P2Y14 receptor antagonist to ameliorate acute gouty arthritis through inhibiting macrophage pyroptosis.

Acute gouty arthritis (AGA) has been classified as an autoinflammatory disease caused by deposition of monosodium urate crystals (MSU), accompanied by swellingofjoint and severe pain. Limited clinical therapy and highincidence indicate that the development of effective drugs for AGA is an urgent need. Our previous study found that P2Y14 receptor (P2Y14R) was a potential target in anti-gout treatment through regulating pyroptosis of macrophages under exposure of MSU. Based on previous work, we carried out further structure modifications and led to a more effective antagonist HQL6 with IC50 of 3.007nM. Extensive profiling of HQL6 has demonstrated that its high selectivity, good pharmacokinetic properties, and reliable in vivo anti-gout efficacy. Moreover, P2Y14R has been demonstrated to be the key target of HQL6 since the diminished effects on adenylate cyclase inhibitor-induced acute gouty arthritis in P2Y14R knockout rats. More importantly, results of single point mutant experiments exhibited that HQL6 might interact with Lys277 as favorable residue in the binding pocket of P2Y14R. Therefore, we confirmed that P2Y14R was a promising drug target for AGA, and HQL6 would be an available candidate for further drug development.

Simulation analysis, properties and applications on a new Burr XII model based on the Bell-X functionalities

<abstract><p>In this article, we make mathematical and practical contributions to the Bell-X family of absolutely continuous distributions. As a main member of this family, a special distribution extending the modeling perspectives of the famous Burr XII (BXII) distribution is discussed in detail. It is called the Bell-Burr XII (BBXII) distribution. It stands apart from the other extended BXII distributions because of its flexibility in terms of functional shapes. On the theoretical side, a linear representation of the probability density function and the ordinary and incomplete moments are among the key properties studied in depth. Some commonly used entropy measures, namely Rényi, Havrda and Charvat, Arimoto, and Tsallis entropy, are derived. On the practical (inferential) side, the associated parameters are estimated using seven different frequentist estimation methods, namely the methods of maximum likelihood estimation, percentile estimation, least squares estimation, weighted least squares estimation, Cramér von-Mises estimation, Anderson-Darling estimation, and right-tail Anderson-Darling estimation. A simulation study utilizing all these methods is offered to highlight their effectiveness. Subsequently, the BBXII model is successfully used in comparisons with other comparable models to analyze data on patients with acute bone cancer and arthritis pain. A group acceptance sampling plan for truncated life tests is also proposed when an item's lifetime follows a BBXII distribution. Convincing results are obtained.</p></abstract>

Factors associated with dissemination and complications of acute bone and joint infections in children

BACKGROUND: Paediatric bone and joint infections remain common in low- and middle-income countries (LMICs) and may have devastating long-term sequelae. There is a paucity of data from LMICs where the true incidence might be underreported, and delayed presentation is common. Our study aimed to determine the complication rate and incidence of disseminated infection in paediatric bone and joint infections in an LMIC setting. Secondly, we aimed to elucidate factors associated with complications and disseminated disease METHODS: We retrospectively reviewed our paediatric orthopaedic database for children that presented with bone and joint infections between September 2015 and March 2019. Data were extracted from medical records, laboratory results and radiological investigations to identify factors that were associated with the development of complications and disseminated infection at a median follow-up of four months RESULTS: We analysed 49 children. The median age at presentation was 6 years (range 1 month to 12 years). Locally advanced disease, with combined acute haematogenous osteomyelitis (AHOM) and septic arthritis (SA), was present in 13 children (27%). The remaining 36 children were evenly divided (18/49 each, 37%) between isolated AHOM and SA, respectively. Disseminated disease was present in 16 children (33%) and was associated with locally advanced disease, an increase in the number of surgeries and an increased length of stay. Twenty-six complications were documented in 22 (45%) children. Chronic osteomyelitis developed in 15/49 (31%) cases, growth arrest in 5/49 (10%), and pathological fracture, DVT and septic shock in 2/49 (4%) each. Complicated disease was associated with locally advanced disease, a higher number of surgeries, disseminated disease and an increased length of stay. Staphylococcus aureus was the infecting pathogen in 65% of cases (31 MSSA, 1 MRSA), while 25% (12/49) were culture-negative infections. While the median time from admission to surgery was one day, the median time from onset of symptoms to surgery was seven days CONCLUSION: We found a high complication rate despite a short follow-up period. More than a quarter of patients had locally advanced disease, and this was associated with the development of complications and disseminated disease. Further studies are needed to be able to predict which children will have poor outcomes Level of evidence: Level 4

Cinnamomi cortex extract mitigated monosodium urate-induced acute gouty arthritis in rats through nuclear factor-κB-NOD-like receptor thermal protein domain associated protein 3 signaling pathway.

Cinnamomi cortex was applied to mitigate joint injury since ancient China. However, the effect of Cinnamomi cortex on gouty arthritis (GA) was rarely reported. This study aimed to explore the effect of Cinnamomi cortex on monosodium urate (MSU)-induced acute GA (AGA) in rats, and clarify the underlying mechanism. The results showed that Cinnamomi cortex extract (CE) containing rich polyphenols and flavonoids alleviated joint swelling and inflammation by reducing programmed cell death in MSU-induced AGA rats. Network pharmacology analysis showed that CE's predictive inflammatory pathways included nuclear factor-κB (NF-κB) and necroptosis pathways. CE reduced expression of pyroptosis-related regulators including Gasdermin D and Caspase 1 via regulating NF-κB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway in AGA rats. In conclusion, this study provided a theoretical basis for Cinnamomi cortex applied as a new veterinary medicine to protect against GA.

Neoisoastilbin Ameliorates Acute Gouty Arthritis via Suppression of the NF-κB/NLRP3 Pathway.

Acute gouty arthritis (AGA) is an acute inflammatory disease, whose occurrence and development mechanism are associated with inflammatory reaction of joint tissue. This study investigated the role of neoisoastilbin (NIA) in the treatment of AGA and explored the underlying mechanisms. C57BL/6 mice underwent intraarticular injection of monosodium urate (MSU) to establish an AGA model in vivo. Enzyme-linked immunosorbent assay, histopathological hematoxylin-eosin staining, western blotting, and other methods were used to observe the therapeutic effects of NIA on AGA and investigate the role of the NF-κB/NLRP3 pathway in the treatment. We found that NIA effectively reduced MSU-induced joint swelling and inflammatory cell infiltration in a concentration-dependent manner. NIA also significantly reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels as compared with the respective values in the model mice group. In addition, administration of NIA significantly mitigated the phosphorylation of NF-κB-related proteins (IKKα, NF-κB, and IκBα) and the expression of NLRP3-related proteins (NLRP3, caspase-1, and ASC) in MSU-induced joint tissues. In conclusion, our research indicated that NIA significantly improved AGA, and its underlying mechanism was achieved by simultaneously inhibiting the NF-κB/NLRP3 pathway and the expression of inflammatory factors. This research preliminarily suggested the potential role of NIA in the treatment of AGA.

Crystal deposition disease as an unusual cause of knee pain in an adult male: Report of a rare case

Abstract Gout is a monosodium urate crystal deposit disease which generally occurs in middle aged male and post-menopausal females. It is typically characterized by episodic acute and chronic arthritis due to deposition of monosodium urate crystals in joints and connective tissue. Palpable deposits of crystals known as tophi may form particularly around joints but also elsewhere. This is a single case based prospective work-up and follow up study done at our institute of a middle-aged male having chronic right knee pain since 1 year year. Meticulous history and clinical examination ,laboratory investigations were done like ESR (erythrocyte sedimentation rate) and CRP (c- reactive protein) and radiological investigation including plain radiograph and MRI (Magnetic resonance imaging) right knee was done and was suggestive of giant cell tumor of patella. Excision and curettage of the lesion was done and sample was sent for HPE (histopathological examination) which showed fibrocartilaginous tissue with features of gouty arthritis. Serum uric acid was done which came out to be raised (10.14 mg/dl). At final follow-up patient had satisfactory outcome. It is important to have in mind that tophus of patella can cause chronic knee pain in patients with gouty arthritis. Early diagnosis and treatment are essential. Patients with tophaceous gout require strict disease control and close follow-up.

Melioidosis-Related Acute Cholangitis and Septic Arthritis.

Melioidosis-Related Acute Cholangitis and Septic Arthritis.

Retracted: Clinical Features and Risk Factors of Fever in Acute Gouty Arthritis.

[This retracts the article DOI: 10.1155/2022/8798838.].

One-Year Follow-Up on Acute Septic Knee Arthritis Treated with XPERIENCE® No-Rinse Solution – A Case Report

One-Year Follow-Up on Acute Septic Knee Arthritis Treated with XPERIENCE® No-Rinse Solution – A Case Report

A mechanically tough and ultra-swellable microneedle for acute gout arthritis.

Acute gout arthritis (AGA) remains the fundamental research focus in the entire medical field. Hydrogel microneedles (HMNs) loaded with therapeutic molecules such as colchicine (Col) have been developed as a new tool for the management of AGA in a minimally invasive manner. However, the incompatible mechanical and swelling properties of HMNs limited the diffusion of the drug from the HMN system, which remains a challenge for practical use. Here, a mechanically tough (11.53 N per needle) and super-swelling (2708%) hydrogel microneedle (HMNs) composed of a uniform network structure was developed using a UV-responsive crosslinker through in situ photopolymerization for percutaneous delivery of Col. Such HMNs and Col loaded HMNs (Col-HMNs) present excellent biocompatibility. Moreover, Col-HMNs present considerable anti-inflammatory effects in vivo through down-regulated inflammatory responses such as related cytokines IL-1β, IL-6, and TNF-α. These results demonstrated that the mechanically tough and super-swelling HMNs could be a promising tool for effective Col delivery to relieve AGA.

The use of Anakinra in treatment of calcium pyrophosphate crystal deposition disease: Analysis of own experience and a literature review

Calcium pyrophosphate crystal deposition disease (CPPD) is a disease caused by the deposition of calcium pyrophosphate crystals, mainly in the articular cartilage, and often manifests as severe acute or chronic arthritis. Therapy given in such cases with non-steroidal anti-inflammatory drugs, colchicine, methotrexate and glucocorticoids is often effective. In these cases, the possibility of prescribing biological drugs, primarily interleukin 1 (IL-1) inhibitors, is being considered. The article analyzes the experience of using Anakinra, an IL-1 receptor antagonist, registered in the Russian Federation in 2021, in 5 patients with persistent arthritis in CPPD. The article also presents an analysis of data from key studies on the use of the drug in patients with CPPD.

Tanshinone IIA Improves Acute Gouty Arthritis in Rats through Regulating Neutrophil Activation and the NLRP3 Inflammasome.

To investigate the prevention and treatment effect of tanshinone IIA (TIIA) on acute gouty arthritis (AGA) and its mechanism. The anti-AGA effect of TIIA was observed in vivo and in vitro. Neutrophils were isolated from the abdominal cavity of mice, and the anti-AGA effect of TIIA was investigated in a rat model of MSU-induced AGA. The pathological changes of the ankle joint tissues were assessed by H&E. Cytokine and chemokine expression were determined by ELISA and RT-qPCR. The NLRP3 inflammasome pathway protein levels in the ankle joint tissues were evaluated via western blotting. Neutrophil migration was evaluated in air pouch and transwell assays. Immunohistochemistry and immunofluorescence analysis evaluate the release of myeloperoxidase (MPO), neutrophil elastase (NE), and citrullination of histone H3 (CitH3). Beclin-1 and LC3B expressions were determined using western blotting and immunofluorescence. Key Findings. Treatment with TIIA alleviated synovial hyperplasia and neutrophil infiltration, regulated cytokine and chemokine expressions, and inhibited NLRP3 activation in AGA rats, neutrophil migration, MPO, NE, and CitH3 expression, and LC3B and Beclin-1 protein expression. These results demonstrate that TIIA can effectively enhance AGA by focusing on the neutrophils and NLRP3 inflammasome, demonstrating that TIIA may act as a potential helpful agent for AGA.