Promising anti-IL-6 therapy for atherosclerosis

Fernández-Ruíz, Irene

doi:10.1038/s41569-021-00575-8

Cited by 5 publications

(4 citation statements)

References 1 publication

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“…CD19+CD20- B cells from vulnerable plaques expressed the pro-inflammatory cytokines IL-6 and TNF-a. IL6 generally was consider to be a pro-atherogenic cytokine that had a strong regulatory effect on the extracellular matrix ( 36 , 37 ). IL-6 stimulates the synthesis of matrix-degrading enzymes that erode the matrix within plaques, leading to the rupture of plaques ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell atlas reveals different immune environments between stable and vulnerable atherosclerotic plaques

et al. 2023

Front. Immunol.

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IntroductionRegardless of the degree of stenosis, vulnerable plaque is an important cause of ischemic stroke and thrombotic complications. The changes of the immune microenvironment within plaques seem to be an important factor affecting the characteristics of the plaque. However, the differences of immune microenvironment between stable and vulnerable plaques were remained unknown.MethodsIn this study, RNA-sequencing was performed on superficial temporal arteries from 5 traumatic patients and plaques from 3 atherosclerotic patients to preliminary identify the key immune response processes in plaques. Mass cytometry (CyTOF) technology was used to explore differences in immune composition between 9 vulnerable plaques and 12 stable plaques. Finally, immunofluorescence technique was used to validate our findings in the previous analysis.ResultsOur results showed that more CD86+CD68+ M1 pro-inflammatory macrophages were found in vulnerable plaques, while CD4+T memory cells were mainly found in stable plaques. In addition, a CD11c+ subset of CD4+T cells with higher IFN-r secretion was found within the vulnerable plaque. In two subsets of B cells, CD19+CD20-B cells in vulnerable plaques secreted more TNF-a and IL-6, while CD19-CD20+B cells expressed more PD-1 molecules.ConclusionIn conclusion, our study suggested that M1-like macrophages are the major cell subset affecting plaque stability, while functional B cells may also contribute to plaque stability.

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Section: Discussionmentioning

confidence: 99%

Single-cell atlas reveals different immune environments between stable and vulnerable atherosclerotic plaques

et al. 2023

Front. Immunol.

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“…[36] Studies have shown that IL6 is directly involved in the inflammatory response of the vascular endothelium, leading to thickening of the intima of arteries and also promotes the expression of intracellular adhesion molecules, which are involved in the formation of atherosclerosis. [37,38] In a state of cerebral ischemia, damaged brain tissue generates an immune response, and inflammatory cells are activated to secrete IL6 as an essential inflammatory mediator involved in secondary brain injury. [39] STAT3 is present in neurons and endothelial cells of blood vessels, astrocytes, and microglia.…”

Section: Discussionmentioning

confidence: 99%

Exploring the active components and mechanism of modified bazhen decoction in treatment of chronic cerebral circulation insufficiency based on network pharmacology and molecular docking

Xu,

Shen,

2023

Medicine

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Modified bazhen decoction (MBZD) is a classical Chinese medicine formula with potential efficacy in the treatment of chronic cerebral circulation insufficiency (CCCI), and its main components and potential mechanisms are still unclear. The study aimed to investigate the active ingredients and mechanism of action of MBZD in treating CCCI through network pharmacology combined with molecular docking. The chemical composition and targets of 11 Chinese herbs in MBZD were retrieved utilizing the traditional Chinese medicine systems pharmacology database and analysis platform platform, and the targets for CCCI were screened by Genecards, online mendelian inheritance in man, therapeutic target database, and comparative toxicogenomics database databases. The targets were genetically annotated with the Uniprot database. We created a compound-target network employing Cytoscape software and screened the core targets for the treatment of CCCI by CytoNCA clustering analysis; the AutoDock Vina program performed molecular docking study of crucial targets. One thousand one hundred ninety-one active compounds were obtained, 2210 corresponding targets were predicted, 4971 CCCI-related targets were obtained, and 136 intersecting genes were identified between them. The central core targets were IL6, MAPK14, signal transducer and activator of transcription 3, RELA, VEGFA, CCND1, CASP3, AR, FOS, JUN, EGFR, MAPK1, AKT1, MYC, and ESR1; gene ontology functional enrichment analysis yielded 911 gene ontology items (P < .01), while Kyoto Encyclopedia of Genes and Genomes pathway enrichment yielded 138 signal pathways (P < .01), primarily including oxidative reactions, vascular regulation, apoptosis, and PI3K-Akt signaling pathway. The molecular docking results showed that the core active component of MBZD had good binding with the main target. This research initially uncovered the mechanism of action of MBZD via multi-component-multi-target-multi-pathway for the treatment of CCCI, providing the theoretical basis for the clinical application of MBZD.

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“…[163] It was worth noting that quercetin, one of the key ingredients of our research, was observed to modulate TNF-α, IL-1β, and IL-6 to treat GA. [137] IL-6 was found to directly participate in the inflammatory response. [164][165][166] Previous research has indicated that Inflammatory cytokines such as IL-6, IL-1, and TNF-α can promote the inflammatory response and joint destruction in patients with arthritis. [167][168][169] One in vivo study found that the expression of IL6 can be significantly reduced by GS.…”

Section: Principal Findingsmentioning

confidence: 99%

Treatment of gouty arthritis with traditional Chinese medicine decoction: Meta-analysis, network pharmacology analysis, and molecular docking

Qu,

Du,

Wang

et al. 2024

Medicine

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Background: Previous studies have shown that traditional Chinese medicine decoction (TCMD) could ameliorate the clinical symptoms and laboratory indicators of gouty arthritis (GA) patients. However, few investigations have been conducted on the efficacy and safety of TCMD for GA, the underlying mechanism of TCMD for GA, and the relationship between the TCMD active ingredients and GA targets. Methods: Randomized controlled trials of TCMD for GA were retrieved from Chinese and English databases. Meta-analysis was conducted by Stata 17 software. Potential sources of heterogeneity were identified through subgroup analysis, meta-regression, and heterogeneity test. Publication bias was assessed by Egger’s test and funnel plots. The ingredients and targets related to TCMD and GA were obtained from multiple databases, such as TCMSP and DrugBank. The protein-protein interaction network, GO and KEGG analysis was constructed using STRING and DAVID. Molecular docking and visualization of the results were completed by AutoDock and PyMOL software. Results: Eighty-four studies were included, involving 7151 patients and 10 outcome indicators. Meta-analysis showed that, compared to routine treatment, TCMD could better reduce the incidence of adverse events and the level of laboratory indicators including blood uric acid (BUA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α). In the section of network pharmacology, we retrieved 150 active ingredients and 303 target genes from the top 10 herbs in 84 studies, as well as 3082 disease targets and 195 cross targets of the herbs and GA. The top ranked ingredients, intersection targets, and signaling pathways included quercetin, kaempferol, and wogonin; AKT1, TNF, and TP53; as well as IL-17, HIF-1, and PI3K-AKT, etc. Among the 81 molecular docking results, we visualized 10 results with low binding energy, including IL1B and beta-sitosterol, MYC and beta-sitosterol, etc. Conclusion: TCMD could be a satisfactory complementary and alternative therapy for GA. However, it should be verified by further studies. Future research could be conducted from the following active ingredients, targets, and signal pathways, such as wogonin, sitosterol, and sitosterol; AKT1, TNF, IL6, and TP53; and IL-17, HIF-1, and PI3K-AKT signaling pathway.

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Promising anti-IL-6 therapy for atherosclerosis

Cited by 5 publications

References 1 publication

Single-cell atlas reveals different immune environments between stable and vulnerable atherosclerotic plaques

Single-cell atlas reveals different immune environments between stable and vulnerable atherosclerotic plaques

Exploring the active components and mechanism of modified bazhen decoction in treatment of chronic cerebral circulation insufficiency based on network pharmacology and molecular docking

Treatment of gouty arthritis with traditional Chinese medicine decoction: Meta-analysis, network pharmacology analysis, and molecular docking

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