Increased Levels of Serum IL-15 and TNF-β Indicate the Progression of Human Intracranial Aneurysm

Yang, Shuzhe; Li, Qingyuan; Yang, Junhua; Wu, Jun; Wang, Shuo

doi:10.3389/fnagi.2022.903619

Cited by 5 publications

(4 citation statements)

References 50 publications

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“…Inflammation within the arterial vessel due to hemodynamic changes is a critical element in the formation of an intracranial aneurysm (IA). [1][2][3][4][5][6][7][8] Understanding the mechanisms leading to the formation of brain aneurysms and identifying all the relevant "players" in this process is essential for the development of an effective pharmacotherapy that could prevent life-threatening subarachnoid hemorrhage from rupture of IA.…”

Section: Introductionmentioning

confidence: 99%

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Kamińska¹,

Maciejczyk²,

Ćwiklińska³

et al. 2022

JIR

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Introduction Identifying all the relevant “players” in the formation and development of brain aneurysms may help understand the mechanisms responsible for the formation of an aneurysm, as well as in the search for non-invasive targets for aneurysm pharmacotherapy. Aim The evaluation of the concentration of pro-inflammatory and anti-inflammatory cytokines in cerebrospinal fluid (CSF) and serum of patients with unruptured intracranial aneurysms (UIA) in comparison to individuals without vascular lesions in the brain. Methods The concentration of 27 proteins in the CSF and serum of UIA patients (N = 40) and individuals without vascular lesions in the brain (N = 15) was evaluated using a multiplex ELISA kit (Bio-Plex Pro Human Cytokine 27-Plex Panel). Results In the CSF 13 out of 27 proteins evaluated presented a concentration 1.36-fold or greater in UIA patients in comparison to the control group. Significantly higher were IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-7, IL-8, IL-12, IL-13, TNF-α, INF-γ, MCP-1, and VEGF. In the serum none of the proteins evaluated significantly differ between UIA patients and the control group. The correlation coefficient analysis showed that CSF IL-1β, IL-8, and TNF-α positively, while IL-13 negatively correlated with the size of aneurysms. CSF IL-6 and MCP-1 concentrations positively correlated with the number of aneurysms. Conclusion In patients with UIA, pro-inflammatory and anti-inflammatory mechanisms are activated simultaneously, because the concentration of promoting and suppressing inflammatory response proteins was significantly higher in CSF of UIA patients compared to the control group. The preventive therapy of brain aneurysm development should be focused on IL-1β, IL-6, IL-8, MCP-1, and TNF-α, the concentration of which in CSF positively correlated with the size and number of aneurysms.

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Section: Introductionmentioning

confidence: 99%

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Kamińska¹,

Maciejczyk²,

Ćwiklińska³

et al. 2022

JIR

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“…Further, the transformation of smooth muscle cells from the contractile phenotype to the proinflammatory/promatrix remodeling type in IA tissues can be considered as response of vascular inflammation [ 26 ]. In addition, elevated levels of inflammatory cytokines and chemokines, such as TNF-α, IL-6 [ 27 , 28 ], and TGF-β [ 29 ], were detected in the blood and cerebrospinal fluid of patients with IA. Taken together, these studies suggest the important role of immune responses in IA formation.…”

Section: Discussionmentioning

confidence: 99%

Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis

Zhou,

Zhu,

Jiang

et al. 2023

Biol Res

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Background Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. Methods The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein–protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. Results In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). Conclusion The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.

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“…Clinical data and cytokines were compared between groups. The study has found elevated levels of IL-15, MCP-1 and TNF-β in UIAs (41). On the other hand, one study used 66 patients with UIAs, 69 patients with RA, and 68 patients with hydrocephalus to perform real-time polymerase reaction to detect cerebrospinal fluid exosome miR-152-3p.…”

Section: Discussionmentioning

confidence: 99%

Identifying and validating key genes mediating intracranial aneurysm rupture using weighted correlation network analysis and exploration of personalized treatment

Wu¹,

Chen²,

Liang³

et al. 2022

Ann Transl Med

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Background: Intracranial aneurysmal subarachnoid hemorrhage (aSAH) is a dangerous and highly fatal condition if ruptured. Significant advances have been made in the treatment of unruptured intracranial aneurysms (UIAs), but risk assessment methods for early diagnosis of intracranial aneurysm (IA) rupture remain limited. Methods:The datasets of IA GSE13353, GSE15629, and GSE54083 were downloaded through the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in unruptured and ruptured aneurysms were identified by R software using methods such as gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the DEGs, and logistic regression models were used to construct a prediction model to discriminate UIA from healthy samples. We then performed GSEA on the genes in the model, followed by model validation using the GSE54083 dataset.Finally, we used the single-sample (ss)GSEA method to investigate the relationship between the diagnostic model genes and immune cells and immune function.Results: A total of 79 DEGs were obtained in patients with IA rupture compared to unruptured controls.The results of KEGG and GO enrichment analysis showed that neutrophil activation is involved in immune response, neutrophil mediated immunity, and positive regulation of angiogenesis. Interestingly, the results of immunoassays demonstrated that the break in IA may be associated with immune T cells. We used DEGs and WGCNA to determine common genes. The logistic regression model was trained based on 24 intersecting genes, and eventually retained 2 genes, KIAA0226L and UPP1, which we found to be reliable using the validation set, and GSEA revealed that the diagnostic model was associated with the Hippo signaling pathway and vascular smooth muscle contraction, and viral protein interaction with cytokine and cytokine were also associated. Finally explored using the CMap database, Tivozanib could be a potential small molecule drug for the treatment of ruptured intracranial aneurysms (RIAs).Conclusions: We identified new diagnostic genes associated with IA rupture, which may provide a new way of aneurysm diagnosis.^ ORCID: 0000-0001-5330-4778.

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Increased Levels of Serum IL-15 and TNF-β Indicate the Progression of Human Intracranial Aneurysm

Cited by 5 publications

References 50 publications

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis

Identifying and validating key genes mediating intracranial aneurysm rupture using weighted correlation network analysis and exploration of personalized treatment

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