Strategies of Targeting Inflammasome in the Treatment of Systemic Lupus Erythematosus

Liu, Yaling; Tao, Xinyu; Tao, Jin‐Hui

doi:10.3389/fimmu.2022.894847

Cited by 8 publications

(11 citation statements)

References 124 publications

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“…The inflammasome and inflammasome-related pathways were here associated with active SLE. Importantly, the inflammasome pathway has been advocated to be relevant in SLE pathogenesis and disease progression,58 59 with therapeutic implications 60. We found that the inhibitory signalling related to cytotoxic T lymphocyte antigen 4 (CTLA-4) was upregulated in SLE patients in LLDAS or DORIS remission.…”

Section: Discussionmentioning

confidence: 93%

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

Parodis,

Lindblom,

Barturen

et al. 2024

Ann Rheum Dis

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ObjectivesTo unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).MethodsWe determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission.ResultsWe analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway.ConclusionsWe demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway differentiation between the two states justifies LLDAS as an acceptable goal from a biological perspective.

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Section: Discussionmentioning

confidence: 93%

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

Parodis,

Lindblom,

Barturen

et al. 2024

Ann Rheum Dis

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“…It has been reported that NF-κB leads to the priming of the inflammasome through transcriptional activation of pro-IL-1β and NLRP3, which in conjunction with an activation signal results in stimulation of the NLRP3 inflammasome. [41][42][43] Such an enhanced inflammatory response contributes to CVD development. Accordingly, clinical trials in which CVD patients are treated with various biologics that target the NLRP3 inflammasome pathway demonstrate a reduction in atherothrombosis.…”

Section: Clinical Trials: Inflammation and Atherosclerosismentioning

confidence: 99%

“…When these autoantibodies interact with their respective antigens this may lead to NF‐κB activation (please refer to the GRP78 and Hsp60 section). It has been reported that NF‐κB leads to the priming of the inflammasome through transcriptional activation of pro‐IL‐1β and NLRP3, which in conjunction with an activation signal results in stimulation of the NLRP3 inflammasome 41–43 . Such an enhanced inflammatory response contributes to CVD development.…”

Section: Introductionmentioning

confidence: 99%

Fatal attractions that trigger inflammation and drive atherosclerotic disease

Sharma,

Mossman,

Austin

2024

Eur J Clin Investigation

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BackgroundAtherosclerosis is the salient, underlying cause of cardiovascular diseases, such as arrhythmia, coronary artery disease, cardiomyopathy, pulmonary embolism and myocardial infarction. In recent years, atherosclerosis pathophysiology has evolved from a lipid‐based to an inflammation‐centric ideology.MethodsThis narrative review is comprised of review and original articles that were found through the PubMed search engine. The following search terms or amalgamation of terms were used: “cardiovascular disease,” “atherosclerosis,” “inflammation,” “GRP78,” “Hsp60,” “oxidative low‐density lipoproteins,” “aldehyde dehydrogenase,” “β2‐glycoprotein,” “lipoprotein lipase A,” “human cytomegalovirus.” “SARS‐CoV‐2,” “chlamydia pneumonia,” “autophagy,” “thrombosis” and “therapeutics.”ResultsEmerging evidence supports the concept that atherosclerosis is associated with the interaction between cell surface expression of stress response chaperones, including GRP78 and Hsp60, and their respective autoantibodies. Moreover, various other autoantigens and their autoantibodies have displayed a compelling connection with the development of atherosclerosis, including oxidative low‐density lipoproteins, aldehyde dehydrogenase, β2‐glycoprotein and lipoprotein lipase A. Atherosclerosis progression is also concurrent with viral and bacterial activators of various diseases. This narrative review will focus on the contributions of human cytomegalovirus as well as SARS‐CoV‐2 and chlamydia pneumonia in atherosclerosis development. Notably, the interaction of an autoantigen with their respective autoantibodies or the presence of a foreign antigen can enhance inflammation development, which leads to atherosclerotic lesion progression.ConclusionWe will highlight and discuss the complex role of the interaction between autoantigens and autoantibodies, and the presence of foreign antigens in the development of atherosclerotic lesions in relationship to pro‐inflammatory responses.

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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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Strategies of Targeting Inflammasome in the Treatment of Systemic Lupus Erythematosus

Cited by 8 publications

References 124 publications

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

Fatal attractions that trigger inflammation and drive atherosclerotic disease

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

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