AI Article Synopsis
- Soluble type II interleukin receptor (sIL1R-II) effectively binds and neutralizes human IL-1beta, presenting potential as an anti-IL-1 therapy.
- Preclinical studies on this receptor have been done in primates, leading to the cloning of monkey IL-1 and IL1R-II for further research.
- Despite the high similarity between human and monkey IL-1beta, the two differ in their interaction with sIL1R-II due to a single amino acid variation.
Article Abstract
Soluble type II interleukin (IL)-1 receptor (sIL1R-II) binds human IL-1beta with high affinity and neutralizes its activity. Recombinant sIL1R-II is considered a potentially useful anti-IL-1 therapeutic, and preclinical studies have been undertaken with this molecule in primates. To better understand the cytokine-receptor interactions occurring in this nonhuman context, monkey IL-1 and IL1R-II were cloned, and their binding abilities were examined in vitro. IL-1beta from cynomolgus monkey was capable of binding and activating the human type I IL-1 receptor. However, unlike human IL-1beta, it was unable to effectively bind and become neutralized by sIL1R-II. Human and cynomolgus IL-1beta proteins are 96% identical, differing by only six amino acids. Structural and mutational analysis revealed that the unique sIL1R-II binding ability of human IL-1beta is due to a single amino acid difference compared with monkey IL-1beta.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M206636200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of RIPK1-driven necroptosis ameliorates inflammatory hyperalgesia caused by lipopolysaccharide: involvement of TLR-, NLRP3-, and caspase-11-mediated signaling pathways.
Cell Mol Biol (Noisy-le-grand)
January 2025
Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Türkiye.
Article Synopsis
- Recent research indicates that blocking the RIPK1/RIPK3/MLKL necrosome can help reduce inflammatory pain linked to conditions like demyelination in the central nervous system.
- This study tests necrostatin-1s (Nec-1s), a specific RIPK1 inhibitor, on LPS-induced inflammatory pain in male mice, assessing pain sensitivity through hot plate tests and examining related protein changes.
- Results show that Nec-1s not only prevents LPS-induced pain relief but also reverses the activation of key proteins and signals involved in inflammation and demyelination, suggesting that RIPK1 inhibitors could be a promising treatment for managing inflammatory pain.
Combination of sST2/LVMI Ratio and Modified MELD Scores Predicts Mortality in End-Stage Heart Failure.
Int J Mol Sci
December 2024
3rd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-007 Katowice, Poland.
Biomarkers are critical for heart failure (HF) management by facilitating risk stratification, therapeutic decision-making, and monitoring treatment response. This prospective, single-center study aimed to assess predictors of death during one-year follow-up in patients with end-stage HF, with particular emphasis on the soluble suppression of tumorigenicity 2/left ventricular mass index (sST2/LVMI) ratio, modified Model for End-stage Liver Disease (modMELD), and Model for End-stage Liver Disease excluding INR (MELD-XI). This study comprised 429 consecutive patients with end-stage HF hospitalized between 2018 and 2023.
View Article and Find Full Text PDFThe Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge.
Int J Mol Sci
December 2024
Nuclear Medicine Department, University of Medicine and Pharmacy "Carol Davila" Bucharest, 050474 Bucharest, Romania.
Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/-T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of I exceeding 150 mCi (5.
View Article and Find Full Text PDFPositive correlation between interleukin (IL) 1 beta to IL-1 receptor antagonist levels in Standardbred racehorses prior to racing.
Vet Immunol Immunopathol
December 2024
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, United States; Pennsylvania Equine Toxicology & Research Laboratory, West Chester, PA 19382, United States. Electronic address:
Interleukin 1 beta (IL-1β) and IL-1 receptor antagonist (IL-1RA) are both upregulated following traumatic injury. As IL-1RA blocks inflammatory signaling by IL-1β, overexpression of IL-1β relative to IL-1RA may drive inflammatory diseases. As such, determination of the relationship between IL-1β to IL-1RA expression levels in horses may provide insight into disease states or serve as a therapeutic readout of response to medical interventions.
View Article and Find Full Text PDFDysregulation of the NLRP3 Inflammasome and Promotion of Disease by IL-1β in a Murine Model of Sandhoff Disease.
Cells
January 2025
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
Sandhoff disease (SD) is a progressive neurodegenerative lysosomal storage disorder characterized by GM2 ganglioside accumulation as a result of mutations in the gene, which encodes the β-subunit of the enzyme β-hexosaminidase. Lysosomal storage of GM2 triggers inflammation in the CNS and periphery. The NLRP3 inflammasome is an important coordinator of pro-inflammatory responses, and we have investigated its regulation in murine SD.
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!