Dulaglutide mitigates inflammatory response in fibroblast-like synoviocytes

Zheng, Weizhuo; Pan, Haile; Li, Wei; Gao, Feng; Lin, Xiaozong

doi:10.1016/j.intimp.2019.05.034

Cited by 24 publications

(22 citation statements)

References 24 publications

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“…As the main cells involved in the pathogenesis, they cause synovial hyperplasia, pannus formation, and cartilage and bone tissue erosion, eventually destroying nearby cartilage and bone tissue ( 2 , 7 ). The hyperproliferating FLSs release a large number of pro-inflammatory indicators, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, causing abnormal inflammation in the synovial membrane ( 8 , 9 ). What is more, the activated FLSs release matrix metalloproteinases (MMPs), which promote FLS migration and invasion ( 10 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

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METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

et al. 2021

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Rheumatoid arthritis (RA), a common autoimmune disease, is extremely damaging to human health. Fibroblast-like synoviocytes (FLSs) have a vital role in the occurrence and development of RA. Methyltransferase-like 3 (METTL3), which is a crucial component of the N6-methyladenosine (m6A) methyltransferase complex, is involved in the progression of many diseases. In this study, we explored the role of METTL3 in the inflammatory response and proliferation, invasion, and migration of FLSs. We used human RA synovial tissues and the adjuvant-induced arthritis (AIA) animal model of RA. Experimental results revealed that METTL3 expression was significantly upregulated in human RA synovial tissues and in the rat AIA model. METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs. In contrast, they were increased by METTL3 overexpression. Additionally, we found that, in FLSs, METTL3 may activate the nuclear factor (NF)-κB signaling pathway. The experimental results showed that METTL3 may promote FLS activation and inflammatory response via the NF-κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

“…What is more, the activated FLSs release matrix metalloproteinases (MMPs), which promote FLS migration and invasion ( 10 , 11 ). Therefore, reducing the activation and inflammatory response of FLSs is a promising therapeutic strategy for the treatment of RA ( 8 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

et al. 2021

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“…Dulaglutide treatment significantly downregulated proinflammatory mediators such as IL-1b, IL-6, MCP-1, HMGB-1, MMP-3 and MMP-13. The effects of dulaglutide were mediated by the inactivation of JNK and increased phosphorylation of IkBa, causing a reduction of NF-kB (144).…”

Section: Glucagon-like Peptide 1 Analoguesmentioning

confidence: 99%

Insulin Signaling in Arthritis

et al. 2021

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Inflammatory arthritis is burdened by an increased risk of metabolic disorders. Cytokines and other mediators in inflammatory diseases lead to insulin resistance, diabetes and hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and hormones. Insulin is produced by pancreatic cells and regulates glucose, fat metabolism and cell growth. The action of insulin is mediated through the insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced cytokine production, proliferation, and migration. In macrophages, defective insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired insulin signaling and arthritis analyzing how insulin signaling may be involved in the aberrant immune response implicated in arthritis and how inflammatory mediators affect insulin signaling. Finally, the effect of glucose-lowering agents on arthritis was summarized.

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“…After 24 h, cells were treated with 1 μg/mL LPS in the presence or absence of aprepitant (5, 10 μM) for 6 h. The luciferase activity of NF-κB was carried out using the commercial kit from Promega, USA according to the manufacturer's instruction. 19…”

Section: Elisamentioning

confidence: 99%

<p>The NK-1R Antagonist Aprepitant Prevents LPS-Induced Oxidative Stress and Inflammation in RAW264.7 Macrophages</p>

Zhao

Bai

et al. 2020

DDDT

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Background: The macrophage is one of the most important types of immune cells that protect against harmful stimuli. Macrophage activation plays a pivotal role in the progression and development of various inflammatory diseases. The neurokinin 1 receptor (NK-1R) is a G protein-coupled receptor that plays an important role in inflammatory diseases. Aprepitant is a kind of NK-1R antagonist. The purpose of this study is to determine the protective effect of aprepitant in lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Methods: We examined the anti-inflammatory and anti-oxidant effects of aprepitant in LPStreated RAW264.7 macrophages by using real-time PCR, ELISA, and Western blot analysis. We also assessed cellular oxidative stress signaling by measuring the levels of cellular MDA, total ROS, and NADPH oxidase expression. Cellular NO production was measured by DAF-FM DA staining. The inhibitory effect of aprepitant against NF-κB signaling was evaluated by luciferase assay and Western blot analysis. Results: The expression of NK-1R is increased in LPS-induced macrophages, suggesting a potential role of the receptor in the inflammatory response. We show that aprepitant protects macrophages against oxidative stress by reducing the generation of ROS and the expression of NOX-4. Furthermore, aprepitant inhibits the secretion of pro-inflammatory cytokines and chemotactic factors by mediating the NF-κB signaling pathway. Conclusion:The NK-1R receptor antagonist aprepitant acts as an anti-inflammatory agent, indicating that the blockage of the NK-1R pathway in macrophages has the potential to suppress inflammation.

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Dulaglutide mitigates inflammatory response in fibroblast-like synoviocytes

Cited by 24 publications

References 24 publications

METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

Insulin Signaling in Arthritis

<p>The NK-1R Antagonist Aprepitant Prevents LPS-Induced Oxidative Stress and Inflammation in RAW264.7 Macrophages</p>

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