Toll-like receptors (TLRs) initiate a signalling cascade via association with an adaptor molecule, myeloid differentiation factor 88 (MyD88) and/or TIR domain-containing adaptor inducing-IFN-beta (Trif), to induce various pro-inflammatory cytokines for microbial eradication. After stimulation of TLR4 with lipopolysaccharide (LPS), both IL-1beta and IL-18 are processed, depending on the activation of caspase-1, although its mechanism remains unclear. ASC is an adapter protein possibly involved in the activation of procaspase-1. To unravel the requirement of ASC, we generated Asc(-/-) mice. Upon stimulation with LPS, Asc(-/-) macrophages failed in the processing of procaspase-1 and maturation of pro-IL-1beta and pro-IL-18, but normally produced other pro-inflammatory cytokines including TNF-alpha and IL-6. MyD88(-/-) and Trif(-/-) macrophages showed normal activation of caspase-1, demonstrating a dispensable role for MyD88 and Trif. After, LPS-challenged Asc(-/-) mice lacked serum elevation of IL-1beta and IL-18. Moreover, the Asc(-/-) mice exhibited neither acute liver injury nor lethal shock. These results demonstrate critical roles for ASC in the release of IL-1beta/IL-18 via activation of caspase-1 and provide new insights into the inflammatory responses for host defence and diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1365-2443.2004.00789.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanism of activation of TLR4/NF-κB/NLRP3 signaling pathway induced by heat stress disrupting the filtration barrier in broiler.
BMC Vet Res
December 2024
College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471000, China.
Background: High-temperature environment can cause acute kidney injury affecting renal filtration function. To study the mechanism of renal injury caused by heat stress through activates TLR4/NF-κB/NLRP3 signaling pathway by disrupting the filtration barrier in broiler chickens. The temperature of broilers in the TN group was maintained at 23 ± 1 °C, and the HS group temperature was maintained at 35 ± 1℃ from the age of 21 days, and the high temperature was 10 h per day, and one broiler from each replicate group at the age of 35 and 42 days was selected for blood sampling, respectively.
View Article and Find Full Text PDFX-ray irradiation reduces ATP-dependent activation of NLRP3 inflammasome by inhibiting TWIK2 activity in macrophages.
Immunol Lett
December 2024
Department of Emergency, Affiliated Hospital of Zunyi Medical University, 563003 Zunyi, Guizhou, China. Electronic address:
Background: The spleen, as the body's largest peripheral immune organ and a crucial source of circulating monocytes, plays a significant role in the acute inflammatory response of spleen-derived macrophages to diseases. Therefore, studying the impact and mechanism of X-ray irradiation on spleen-derived macrophages' inflammatory responses is of great importance.
Method: Extracted and identified mice splenic macrophages were divided into four groups: control group, LPS and ATP co-stimulated non-irradiated group, LPS and ATP co-stimulated group irradiated after 6h, and LPS and ATP co-stimulated group irradiated after 12h.
Macrophage NLRP3-dependent IL-1β production contributes to aortic fibrosis in heart failure with preserved ejection fraction.
Acta Biochim Biophys Sin (Shanghai)
December 2024
Fibrosis is the main pathological feature of aortic stiffness, which is a common extracardiac comorbidity of heart failure with preserved ejection fraction (HFpEF) and a contributor to left ventricular (LV) diastolic dysfunction. Systemic low-grade inflammation plays a crucial role in the pathogenesis of HFpEF and the development of vascular fibrosis. In this study, we investigate the inflammatory mechanism of aortic fibrosis in HFpEF using a novel mouse model.
View Article and Find Full Text PDFFibroblast Growth Factor 21 Confers Protection Against Asthma Through Inhibition of NLRP3 Inflammasome Activation.
Inflammation
December 2024
Department of Pediatrics, Xijing Hospital, the Fourth Military Medical University, No.127 Changle West Road, Xi'an, 710032, China.
Fibroblast growth factor 21 (FGF21) modulates the inflammatory response in a range of pathological conditions. However, whether FGF21 modulates asthma remains unexplored. This study sought to investigate its function in asthma using an ovalbumin (OVA)-induced mouse model.
View Article and Find Full Text PDFTargeted isolation of diketopiperazines from a deep-sea derived fungus with anti-neuroinflammatory effects.
Bioorg Chem
December 2024
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Ningbo Institute of Marine Medicine, Peking University, Beijing 100191, PR China. Electronic address:
Prenylated indole diketopiperazines represent a diverse array of alkaloids with complex chemical scaffolds and with a wide range of biological activities. Aiming to discover bioactive metabolites with structural novelty, genomic annotation in association with the MS/MS-based molecular networking demonstrated a deep-sea derived fungus Aspergillus puulaauensis F77 containing a profile of diketopiperazines. Targeted separation of the cultured fungus led to the isolation of 19 undescribed austamide-type diketopiperazines namely versicoines A-S.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!