Dexamethasone, a corticosteroid, has been approved for use in the treatment of severe COVID-19, which is characterised by hyperinflammation and associated lung damage. However, dexamethasone shows no clinical benefit in the treatment of less severe disease, and prolonged treatment may lead to immunosuppression and an increased risk of opportunistic infections. Hence there is a need for more specific anti-inflammatory therapies which also prevent severe disease. The NLRP3 inflammasome is an intracellular signalling complex which is responsible for the cleavage and release of the cytokines IL-1β and IL-18 and has also been shown to be inhibited by dexamethasone. NLRP3 inflammasome activation is strongly correlated with COVID-19 severity and part of dexamethasone's clinical effect in COVID-19 may be via NLRP3 inhibition. Specific NLRP3 inhibitors are currently undergoing clinical trials for the treatment of COVID-19. In this review, we evaluate the evidence supporting the use of dexamethasone and speculate on the potential use of NLRP3 inhibitors to treat COVID-19 as a more specific approach that may not have the liabilities of dexamethasone.
Part I: Methods to Detect and Analyze Toll-Like Receptors 1 Expression Analysis of the Toll-Like Receptors in Human Peripheral Blood Mononuclear Cells Jakub Siednienko and Sinead M. Miggin 2 Ligands, Cell-Based Models and Readouts Required for Toll-Like Receptor Action Jerome Dellacasagrande 3 Toll-Like Receptor Interactions Imaged by FRET Microscopy and GFP Fragment Reconstitution Gabor Horvath, Scott Young, and Eicke Latz 4 Predicting Toll-Like Receptor Structures and Characterizing Ligand Binding Joshua N. Leonard, Jessica K. Bell, and David M. Segal 5 Bioinformatic Analysis of Toll-Like Receptor Sequences and Structures Tom P. Monie, Nicholas J. Gay, and Monique Gangloff 6 Expression, Purification and Crystallization of Toll/Interleukin-1 Receptor (TIR) Domains Xiao Tao and Liang Tong Part II: Methods to Analyze Signal Transduction Downstream of Toll-Like Receptor Stimulation 7 Proteomic Analysis of Protein Complexes in Toll-Like Receptor Biology Kiva Brennan and Caroline A. Jefferies 8 2D-DIGE Comparative Proteomics: Investigation of the Proteome in Cellular Signalling Pathways Nadia Ben Larbi and Caroline A. Jefferies 9 MAPPIT (Mammalian Protein-Protein Interaction Trap) Analysis of Early Steps in Toll-Like Receptor Signalling Peter Ulrichts, Irma Lemmens, Delphine Lavens, Rudi Beyaert, and Jan Tavernier 10 Analysis of the Functional Role of Toll-Like Receptor-4 Tyrosine Phosphorylation Andrei E. Medvedev and Wenji Piao 11 Analysis of Ubiquitin Degradation and Phosphorylation of Proteins Pearl Gray 12 The Generation of Highly Purified Primary Human Neutrophils and Assessment of Apoptosis in Response to Toll-Like ReceptorLigands Lisa C. Parker, Lynne R. Prince, David J. Buttle, and Ian Sabroe 13 Cellular Expression of A20 and ABIN-3 in Response to Toll-Like Receptor-4 Stimulation Kelly Vershelst, Lynn Verstrepen, Beatrice Coornaert, Isabelle Carpentier, and Rudi Beyaert 14 Characterisation of Viral Proteins that Inhibit Toll-Like Receptor Signal Transduction Julianne Stack and Andrew G. Bowie Part III: Genetic Techniques in Toll-Like Receptor Analysis 15 Genetic Dissection of Toll-Like Receptor Signaling Using ENU Mutagenesis Kasper Hoebe 16 Microarray Experiments to Uncover Toll-Like Receptor Function Harry Bjorkbacka 17 Uncovering Novel Gene Function in Toll-Like Receptor Signalling Using siRNA Michael Carty, Sinead Keating, and Andrew G. Bowie 18 Genotyping Methods to Analyze Polymorphisms in Toll-Like Receptors and Disease Chiea-Chuen Khor Part IV: Toll-Like Receptors and Disease 19 Experimental Models of Acute Infection and Toll-Like Receptor Driven Septic Shock Ruth Ferstl, Stephan Spiller, Sylvia Fichte, Stefan Dreher, and Carsten J. Kirschning 20 Toll-Like Receptors and Rheumatoid Arthritis Fabia Brentano, Diego Kyburz, and Steffen Gay 21 Practical Techniques for Detection of Toll-Like Receptor-4 in the Human Intestine Ryan Ungaro, Maria T. Abreu, and Masayuki Fukata 22 Toll-Like Receptor-Dependent Immune Complex Activation of B Cells and Dendritic Cells Melissa B. Uccellini, Ana M. Avalos, Ann Marshak-Rothstein, and Gregory A. Viglianti 23 Innate Immunity, Toll-Like Receptors and Atherosclerosis: Mouse Models and Methods Rosalinda Sorrentino and Moshe Arditi 24 Generation of Parasite Antigens for Use in
No abstract is provided for this article.
Toll-like receptors (TLRs) provoke a profound inflammatory response during host defense and must be controlled in order to avoid autoimmune and inflammatory diseases. In this issue, Rothlin et al. (2007) uncover a complex negative feedback mechanism to limit TLR signaling involving the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases, which induce expression of the inhibitory proteins SOCS1 and SOCS3.
Conference Abstract| February 01 1999 Hyaluronic Acid Fragments Activate NFκB in ECV304 Cells Via Its Principal Cell Surface Receptor CD44 K. A. Fitzgerald; K. A. Fitzgerald 1Department of Biochemistry & Biotechnology Institute, Trinity College, Dublin 2, Ireland Search for other works by this author on: This Site PubMed Google Scholar L. A. J. O'Neill L. A. J. O'Neill 1Department of Biochemistry & Biotechnology Institute, Trinity College, Dublin 2, Ireland Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1999 Biochemical Society1999 Biochem Soc Trans (1999) 27 (1): A43. https://doi.org/10.1042/bst027a043a Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation K. A. Fitzgerald, L. A. J. O'Neill; Hyaluronic Acid Fragments Activate NFκB in ECV304 Cells Via Its Principal Cell Surface Receptor CD44. Biochem Soc Trans 1 February 1999; 27 (1): A43. doi: https://doi.org/10.1042/bst027a043a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1999 Biochemical Society1999 Article PDF first page preview Close Modal You do not currently have access to this content.
No abstract is provided for this article.
The infiltration of leukocytes into the central nervous system is associated with many pathologic conditions of the brain. The mechanisms by which these immune cells can penetrate the blood-brain barrier and remain within the brain are not understood. However, elevated brain levels of the pro-inflammatory cytokine IL-1 appear to accompany pathogenesis. The present study provides the first evidence that IL-1 can induce the expression of adhesion molecules for leukocytes on glial cells and suggests a role for the transcription factor NF-kappa B in the induction process. Human rIL-1 alpha was found to induce the expression of the cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) but not E-selectin in human 1321N1 astrocytoma. Both VCAM-1 and ICAM-1 were detectable from 3 h and remained sustained for up to 72 h. Induction was inhibited by the IL-1 receptor antagonist. IL-1 alpha was also shown to induce the expression of VCAM-1 and ICAM-1 in a receptor-dependent fashion in human A172 glioblastoma. Activation of the transcription factor NF-kappa B was also observed in 1321N1 astrocytoma in response to IL-1 alpha treatment and was similarly abolished by pretreatment of cells with antagonist. Activated NF-kappa B was apparent from 20 min and remained for up to 24 h. N-acetylcysteine (NAC) and pyrollidinedithiocarbamate (PDTC), which were shown to inhibit activation of NF-kappa B in Jurkat E6.1 lymphoblasts and EL4.NOB-1 thymoma, failed to block IL-1 activation of NF-kappa B in 1321N1 astrocytoma. However, both of these antioxidants demonstrated complex modulatory effects on the induction of cell adhesion molecule expression by IL-1. The induction of VCAM-1 but not of ICAM-1 proved susceptible to inhibition by both PDTC and NAC. The expression of adhesion molecules for leukocytes on glial cells in response to IL-1 may represent an important mechanism for retention of immune cells in the central nervous system that may be a prologue to inflammatory conditions in the brain.
No abstract is provided for this article.
Innate immunity to viruses involves receptors such as RIG-I, which senses viral RNA and triggers a signalling pathway involving the outer mitochondrial membrane protein MAVS. Recent work has identified that NLRX1, a member of another class of innate immune receptors, sequesters MAVS away from RIG-I and thereby prevents mitochondrial anti-viral immunity.
