Activation of NLRP3 Inflammasome in the Skin of Patients with Systemic and Cutaneous Lupus Erythematosus

Mähönen, Katariina; Hau, Annika; Bondet, Vincent; Duffy, Darragh; Eklund, Kari K.; Panelius, Jaana; Ranki, Annamari

doi:10.2340/actadv.v102.2293

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…OAS3 is a member of the 2’-5’-oligoadenylate synthetase family and is involved in immune responses, which could restrict the replication of certain types of viruses ( 62 , 63 ). Interferon-induced protein with tetratricopeptide repeats (IFIT) 1 is a member of the IFIT family and plays an important role in antiviral processes, and research has revealed that IFIT1 is involved in the development of systemic lupus erythematosus (SLE) ( 64 , 65 ). Interferon-induced protein 44-like is an interferon-induced gene overexpressed in patients with SLE that might be a drug target of SLE ( 66 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Chen

Ouyang²,

Fang³

et al. 2022

Front. Cardiovasc. Med.

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ObjectivesThe mortality rate of abdominal aortic aneurysm (AAA) is extremely high in the older population. This study aimed to identify potential biomarkers of AAA and aortic rupture and analyze infiltration of immune cells in stable and ruptured AAA samples.MethodsRaw data of GSE47472, GSE57691, and GSE98278 were downloaded. After data processing, the co-expression gene networks were constructed. Gene Ontology and pathway enrichment analysis of AAA- and aortic rupture-related gene modules were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for further enrichment analysis. The CIBERSORT tool was used to analyze the relative abundance of immune cells in samples. Differentially expressed immune-related genes were analyzed between different samples. Predictive models were constructed via extreme gradient boosting, and hub genes were identified according to feature importance.ResultsBlue and yellow modules were significantly related to AAA, and genes in these modules were associated with the aortic wall and immune response, respectively. In terms of aortic rupture, the most relevant module was significantly enriched in the inflammatory response. The results of GSEA and GSVA suggested that immune cells and the inflammatory response were involved in the development of AAA and aortic rupture. There were significant differences in the infiltration of immune cells and expression levels of immune-related genes among different samples. NFKB1 might be an important transcription factor mediating the inflammatory response of AAA and aortic rupture. After the construction of a predictive model, CD19, SELL, and CCR7 were selected as hub genes for AAA whereas OAS3, IFIT1, and IFI44L were identified as hub genes for aortic rupture.ConclusionWeakening of the aortic wall and the immune response both contributed to the development of AAA, and the inflammatory response was closely associated with aortic rupture. The infiltration of immune cells was significantly different between different samples. NFKB1 might be an important transcription factor in AAA and aortic rupture. CD19, SELL, and CCR7 had potential diagnostic value for AAA. OAS3, IFIT1, and IFI44L might be predictive factors for aortic rupture.

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Section: Discussionmentioning

confidence: 99%

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Chen

Ouyang²,

Fang³

et al. 2022

Front. Cardiovasc. Med.

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“…When compared to non-atherosclerotic arteries, atherosclerotic vessels have considerably higher levels of IL1B expression, which concurrently promotes the development of AS plaque. 21 Additionally, IL1B expression was found to be elevated in SLE patients, 22 which promotes the production of IFN-γ by CD4+ T cells mainly through an autocrine manner, 23 while serum IFN-γ is a potential biomarker of SLE disease activity. 24 The studies mentioned above are consistent with the findings of this research and provide more evidence for the viability of AQP9, CCR1, CD83, CXCL1, FCGR2A, IL1RN, IL1B, and TNF as targets for the diagnosis and treatment of SLE and AS.…”

Section: Discussionmentioning

confidence: 99%

The exploration of shared genes and molecular mechanisms of systemic lupus erythematosus and atherosclerosis

Fan

Zhu

et al. 2022

Lupus

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Objective Despite widespread recognition, the mechanisms underlying the relationship between systemic lupus erythematosus (SLE) and atherosclerosis (AS) are still unclear. Our study aimed to explore the shared genetic signature and molecular mechanisms of SLE and AS using a bioinformatics approach. Methods Gene expression profiles of GSE50772 (contains peripheral blood mononuclear cells from 61 SLE patients and 20 normal samples) and GSE100927 (contains 69 AS plaque tissue samples and 35 control samples) were downloaded from the Gene Expression Database (GEO) before the differentially expressed genes were obtained using the “limma” package in R. The differential genes were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the DAVID online platform to annotate their functions. The intersection targets of PPI and WGCNA were used as key shared genes for SLE and AS with their diagnostic value as shared genes being verified through ROC curves. Finally, Cytoscape 3.7.2 software was used to construct a miRNA-mRNA network map associated with the shared genes. Results A total of 246 DEGs were identified, including 189 upregulated genes and 57 downregulated genes, which were mainly enriched in signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and NF-kB signaling pathway. The molecular basis for the relationship between SLE and AS may be the aforementioned signaling pathways. Following ROC curve validation, the intersection of PPI and WGCNA, as well as AQP9, CCR1, CD83, CXCL1, and FCGR2A, resulted in the identification of 15 shared genes. Conclusion The study provided a new perspective on the common molecular mechanisms between SLE and AS, and the key genes and pathways that were identified as being part of these pathways may offer fresh perspectives and suggestions for further experimental research.

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“…Canonical inflammasomes are involved in the pathogenesis of SLE and lupusrelated diseases such as lupus nephritis and are regarded as potential targets for SLE treatment [82][83][84][85][86]. Recent studies have also reported the regulatory role of non-canonical inflammasomes in SLE pathogenesis.…”

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases

2024

IJMS

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Inflammasomes are intracellular multiprotein complexes that activate inflammatory signaling pathways. Inflammasomes comprise two major classes: canonical inflammasomes, which were discovered first and are activated in response to a variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and non-canonical inflammasomes, which were discovered recently and are only activated in response to intracellular lipopolysaccharide (LPS). Although a larger number of studies have successfully demonstrated that canonical inflammasomes, particularly the NLRP3 inflammasome, play roles in various rheumatic diseases, including rheumatoid arthritis (RA), infectious arthritis (IR), gouty arthritis (GA), osteoarthritis (OA), systemic lupus erythematosus (SLE), psoriatic arthritis (PA), ankylosing spondylitis (AS), and Sjögren’s syndrome (SjS), the regulatory roles of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 non-canonical inflammasomes, in these diseases are still largely unknown. Interestingly, an increasing number of studies have reported possible roles for non-canonical inflammasomes in the pathogenesis of various mouse models of rheumatic disease. This review comprehensively summarizes and discusses recent emerging studies demonstrating the regulatory roles of non-canonical inflammasomes, particularly focusing on the caspase-11 non-canonical inflammasome, in the pathogenesis and progression of various types of rheumatic diseases and provides new insights into strategies for developing potential therapeutics to prevent and treat rheumatic diseases as well as associated diseases by targeting non-canonical inflammasomes.

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Activation of NLRP3 Inflammasome in the Skin of Patients with Systemic and Cutaneous Lupus Erythematosus

Cited by 11 publications

References 42 publications

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

Identification of biomarkers and analysis of infiltrated immune cells in stable and ruptured abdominal aortic aneurysms

The exploration of shared genes and molecular mechanisms of systemic lupus erythematosus and atherosclerosis

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases

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