Dataset Information

Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine.

ABSTRACT: Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.

SUBMITTER: Lee D

PROVIDER: S-EPMC10341941 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine.

Lee Dongun D Hong Jeong Hee JH

International journal of molecular sciences 20230628 13

Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a gr ...[more]

PMID: 37445932

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Project description:ObjectiveRheumatoid arthritis (RA) is a prevalent autoimmune disorder that leads to chronic joint inflammation, deformity, disability, and systemic complications. This study aimed to analyze the clinical characteristics and synovial pathology of RA patients with synoviocyte detachment, and explore the factors associated with this phenomenon.MethodsThis was a retrospective cohort study included RA patients who underwent synovial biopsy at our center from April to September 2023. Demographic, clinical, laboratory, and synovial histological data were retrospectively collected from medical records at the time of joint synovial biopsy in patients. Microscopic examination of hematoxylin and eosin (HE)-stained synovial tissue sections categorized the samples into synoviocyte detachment and no-synoviocyte detachment groups. Clinical characteristics and synovial pathological changes were compared between the two groups, and the factors associated with synoviocyte detachment were explored through logistic regression analysis.ResultsFifty-five RA patients were enrolled; 45 were females, and the mean age was 53.4 ± 11.8 years. Nine RA patients exhibited synoviocyte detachment. A total of 46 RA patients in the no-synoviocyte detachment group (15 with a normal lining layer and 31 with synovial cell proliferation) were included. Compared with the no-synoviocyte detachment group, the synoviocyte detachment group presented higher RF, ESR, CRP and DAS28-CRP levels (P < 0.05). The synoviocyte detachment group exhibited more prominent neovascularization (P < 0.05). ESR, DAS28-CRP and synovial neovascularization were risk factors associated with synoviocyte detachment in RA patients.ConclusionRA patients with synoviocyte detachment exhibit elevated clinical disease activity, marked by pronounced synovial pathology featuring increased neovascularization and less inflammatory cell infiltration. A significant reduction in lymphocyte count compared with patients with synovial cell proliferation was also observed.

Project description:Background: Ischemia-reperfusion injury (I/R) strongly affects the prognosis of children with complicated congenital heart diseases (CHDs) who undergo long-term cardiac surgical processes. Recently, the α2-adrenergic receptor agonist Dexmedetomidine (Dex) has been reported to protect cardiomyocytes (CMs) from I/R in cellular models and adult rodent models. However, whether and how Dex may protect human CMs in young children remains largely unknown. Methods and Results: Human ventricular tissue from tetralogy of Fallot (TOF) patients and CMs derived from human-induced pluripotent stem cells (iPSC-CMs) were used to assess whether and how Dex protects human CMs from I/R. The results showed that when pretreated with Dex, the apoptosis marker-TUNEL and cleaved caspase 3 in the ventricular tissue were significantly reduced. In addition, the autophagy marker LC3II was significantly increased compared with that of the control group. When exposed to the hypoxia/reoxygenation process, iPSC-CMs pretreated with Dex also showed reduced TUNEL and cleaved caspase 3 and increased LC3II. When the autophagy inhibitor (3-methyladenine, 3-MA) was applied to the iPSC-CMs, the protective effect of Dex on the CMs was largely blocked. In addition, when the fusion of autophagosomes with lysosomes was blocked by Bafilomycin A1, the degradation of p62 induced by Dex during the autophagy process was suspended. Moreover, when pretreated with Dex, both the human ventricle and the iPSC-CMs expressed more AMP-activated protein kinase (AMPK) and phospho AMPK (pAMPK) during the I/R process. After AMPK knockout or the use of an α2-adrenergic receptor antagonist-yohimbine, the protection of Dex and its enhancement of autophagy were inhibited. Conclusion: Dex protects young human CMs from I/R injury, and α2-adrenergic receptor/AMPK-dependent autophagy plays an important role during this process. Dex may have a therapeutic effect for children with CHD who undergo long-term cardiac surgical processes.

Dataset Information

Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine.

Publications

Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine.

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