- |||||||||| Complement-Driven Type-I IFN Response Enhances mTOR Activation and T-Cell Immunity (Poster hall) - Mar 16, 2024 - Abstract #CROI2024CROI_1131;
The potential for myeloid cells to act as bona fide targets of SARS-CoV-2 infection remains unclear. Here, we show that complement-opsonized SARS-CoV-2 induces type I IFN secretion, upregulates the mTOR pathway and directly activates NLRP3, which leads to IL-1
- |||||||||| Journal: Anaphylactic degranulation by mast cells requires the mobilization of inflammasome components. (Pubmed Central) - Mar 15, 2024
was rapidly packaged into granules after IgE-Ag stimulation and processed within granule remnants by proteases after degranulation, causing lethal anaphylaxis in mice. During IgE-Ag-mediated degranulation of endotoxin-primed MCs, granulosomes promoted degranulation, combined with exteriorization and processing of IL-1?, resulting in severe inflammation.
- |||||||||| Journal: mTORC1 accelerates osteosarcoma progression via m6A-dependent stabilization of USP7 mRNA. (Pubmed Central) - Mar 12, 2024
Our results demonstrated that E2-activtated mTORC1 promoted USP7 stability, which promoted OS cell proliferation and migration via upregulating NLRP3 expression and enhancing NLRP3 inflammasome signaling pathway. These results discover a novel mechanism of E2 regulating OS progression and provide a promising therapeutic target for OS progression.
- |||||||||| Kineret (anakinra) / SOBI
Journal: P2X7 receptor inhibition alleviates mania-like behavior independently of interleukin-1?. (Pubmed Central) - Mar 6, 2024 We tested in a mouse model of the subchronic amphetamine (AMPH)-induced hyperactivity whether P2X7R inhibition alleviated mania-like behavior through IL-1?...The NLRP3 inhibitor MCC950 failed to reduce AMPH-induced locomotion in WT mice, whereas the IL-1 receptor antagonist anakinra slightly increased it...In wild-type and IL-1?/?-knockout female mice, JNJ-47965567 was also effective in attenuating AMPH-induced hyperlocomotion. This study suggests that AMPH-induced hyperactivity is modulated by P2X7Rs, but not through IL-1?.
- |||||||||| Journal: NLRP3 inhibition leads to impaired mucosal fibroblast function in patients with inflammatory bowel diseases. (Pubmed Central) - Mar 4, 2024
These data show that AA is an important physiological regulator of the NLRP3 inflammasome and explains why fasting reduces systemic inflammation and also suggests a mechanism to explain how nonsteroidal anti-inflammatory drugs work. In the presented study, we demonstrate that inhibiting NLRP3 might pave the way for novel therapeutic approaches in IBD, especially to prevent the severe complication of intestinal fibrosis formation.
- |||||||||| Review, Journal: New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation. (Pubmed Central) - Feb 29, 2024
This review gives an overview of the established NLRP3 inflammasome assembly, its brief molecular mechanistic activations as well as a current update on specific and non-specific NLRP3 inhibitors that could be used in NLRP3-mediated diseases. We also focused on the recently discovered epigenetic mechanisms mediated by DNA methylation, histone alterations, and microRNAs in regulating the activation and expression of NLRP3 inflammasome, which has resulted in a novel method of gaining insight into the mechanisms that modulate NLRP3 inflammasome activity and introducing potential therapeutic strategies for CNS disorders.
- |||||||||| Journal: HIV Infection Drives Foam Cell Formation via NLRP3 Inflammasome Activation. (Pubmed Central) - Feb 28, 2024
This study suggests that HIV itself may contribute to increased CVD risk in PWH. Understanding the involvement of the inflammasome pathway in HIV atherosclerosis can help identify potential therapeutic targets to mitigate cardiovascular risks in PWH.
- |||||||||| fluoxetine / Generic mfg.
Preclinical, Journal: Antidepressant effects of Parishin C in chronic social defeat stress-induced depressive mice. (Pubmed Central) - Feb 26, 2024 This effect appears to be mediated by the normalization of neurotransmitter and corticosterone levels, inhibition of NLRP3 inflammasome activation. This newfound antidepressant property of Par offers a novel perspective on its pharmacological effects, providing valuable insights into its potential therapeutic and preventive applications in depression treatment.
- |||||||||| colchicine / Generic mfg.
Journal: A novel NLRP3 inhibitor as a therapeutic agent against monosodium urate-induced gout. (Pubmed Central) - Feb 23, 2024 The number and height of intestinal villi were decreased by colchicine but not by SLC3037. SLC3037, a NLRP3 inhibitor blocking NEK7 binding to NLRP3, could be a novel agent against diseases associated with NLRP3 inflammasome activation such as gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.
- |||||||||| Transfer RNA (tRNA) Methylation Preserves Inflammasome Function During Cellular Stress (San Diego Convention Center, Room 1A-B (Upper Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_7363;
TRMT1 is upregulated in bacterial pneumonia, methylates specific tRNAs, and prevents tRNA fragmentation. Exposure to cellular stressors leads to the formation of biologically active tRNA-derived fragments, which subsequently inhibit NLRP3 protein production.
- |||||||||| Association of Sodium-glucose Cotransporter 2 (SGLT-2) Inhibitor Use and Chronic Obstructive Pulmonary Disease (COPD) Outcomes Amongst Patients With Type 2 Diabetes Mellitus (San Diego Convention Center, Area I (Hall H, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_6302;
The rationale behind these results could be explained by the literature evidence of reduced proinflammatory markers and increased anti-inflammatory markers seen with SGLT-2i use in T2DM patients via inhibition of NLRP3 inflammasome activation in multiple tissues including heart, liver, kidney and lungs. Given the increased risk of COPD exacerbations in T2DM patients, further prospective studies to understand the beneficial effects of SGLT-2i use in COPD will help develop more management strategies to prevent the progression of inflammation and disease activity amongst COPD patients with T2DM.
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