Cytokines receptors exist in membrane bound and soluble form. A soluble form of the human IL-6R is generated by limited proteolysis and alternative splicing. The complex of IL-6 and soluble IL-6R stimulates target cells not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. We have named this process trans-signaling. Soluble gp130 is the natural inhibitor of IL-6/soluble IL-6R complex responses. Recombinant soluble gp130 protein is a molecular tool to discriminate between gp130 responses via membrane bound and soluble IL-6R responses. Neutralizing monoclonal antibodies for global blockade of IL-6 signaling and the sgp130Fc protein for selective blockade of IL-6 trans-signaling have been used in several animal models of human diseases. Using the sgp130Fc protein or sgp130Fc transgenic mice we demonstrate in models of inflammatory bowel disease, peritonitis, rheumatoid arthritis, atherosclerosis pancreatitis, colon cancer, ovarian cancer and pancreatic cancer, that IL-6 trans-signaling via the soluble IL-6R is the crucial step in the development and the progression of the disease. Therefore, sgp130Fc is a novel therapeutic agent for the treatment of chronic inflammatory diseases and cancer and it undergoes phase I clinical trials as an anti-inflammatory drug since June 2013.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.smim.2013.11.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Toledo/College of Pharmacy, Toledo, OH, USA.
Background: Primary cilia are solitary membrane-bound organelles emanating from the apical surface of most mammalian cells. They serve as sensory organelles sampling the extracellular environment and reprogramming the transcriptional machinery in response to changes in fluid flow. Ciliopathies, a group of genetic disorders characterized by disrupted cilia structure and/or function, share common phenotypes such as vascular dysfunction and cognitive impairment.
View Article and Find Full Text PDFCapsular Polysaccharide Restrains Type VI Secretion in .
Elife
January 2025
Laboratory of Molecular Microbiology, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
The type VI secretion system (T6SS) is a sophisticated, contact-dependent nanomachine involved in interbacterial competition. To function effectively, the T6SS must penetrate the membranes of both attacker and target bacteria. Structures associated with the cell envelope, like polysaccharides chains, can therefore introduce spatial separation and steric hindrance, potentially affecting the efficacy of the T6SS.
View Article and Find Full Text PDFRational design of stable carbon nitride monolayer membranes for highly controllable CO capture and separation from CH and CH.
Nanoscale
January 2025
Advanced Materials Science Innovation Center, Longmen Laboratory, Luoyang 471003, China.
CO capture and separation from natural and fuel gas are important industrial issues that refer to the control of CO emissions and the purification of target gases. Here, a novel non-planar g-CN monolayer that could be synthesized the supramolecular self-assembly strategy was identified using DFT calculations. The cohesive energy, phonon spectrum, BOMD, and mechanical stability criteria confirm the stability of the g-CN monolayer.
View Article and Find Full Text PDFStructural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase.
Nat Commun
January 2025
Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5'-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) that are the main phospholipids in eukaryotic cells.
View Article and Find Full Text PDFPolyolefin reweaved ultra-micropore membrane for CO capture.
Nat Commun
January 2025
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing, China.
High-performance gas separation membranes have potential in industrial separation applications, while overcoming the permeability-selectivity trade-off via regulable aperture distribution remains challenging. Here, we report a strategy to fabricate Polyolefin Reweaved Ultra-micropore Membrane (PRUM) to acquire regulable microporous channel. Specifically, olefin monomers are dispersed uniformly into a pristine membrane (e.
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!