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No abstract is provided for this article.
No abstract is provided for this article.
A study of human B lymphocytes identifies an important synergy between NOD1 or NOD2 and TLRs in proliferation and activation.
Four families of PRRs (pattern-recognition receptors) have been identified as important components of innate immunity, participating in the sensory system for host defence against the invasion of infectious agents. The TLRs (Toll-like receptors) recognize a variety of conserved microbial PAMPs (pathogen-associated molecular patterns) derived from bacteria, viruses, protozoa and fungi. They work in synergy with the cytosolic NLRs [NOD (nucleotide binding and oligomerization domain)-like receptors] (which sense bacteria), RLRs [RIG-I (retinoic acid-inducible gene 1)-like receptors] (which sense viruses) and CLRs (C-type lectin receptors) (which sense fungi). All of these receptor families signal an increase in the expression of a range of immune and inflammatory genes. The structural architecture of these receptors is conserved, involving seven distinct domains: the LRR (leucine-rich repeat) domain, the TIR [Toll/IL (interleukin)-1 receptor] domain, the NBS (nucleotide-binding site), the CARD (caspase recruitment domain), the PYD (pyrin domain), the helicase domain and the CTLD (C-type lectin domain). Two other domains, the Ig domain and the ITAM (immunoreceptor tyrosine-based activation motif) domain also participate and are also found in antibodies and TCRs (T-cell receptors), key proteins in adaptive immunity. This total of nine domains can therefore be used to construct immune systems which are common to many, if not all, species, allowing us to speculate on the minimum requirement for a complex immune system in structural terms. These insights are important for our overall understanding of the regulation of immunity in health and disease.
Recent studies on intracellular metabolism in dendritic cells (DCs) and macrophages provide new insights on the functioning of these critical controllers of innate and adaptive immunity. Both cell types undergo profound metabolic reprogramming in response to environmental cues, such as hypoxia or nutrient alterations, but importantly also in response to danger signals and cytokines. Metabolites such as succinate and citrate have a direct impact on the functioning of macrophages. Immunogenicity and tolerogenicity of DCs is also determined by anabolic and catabolic processes, respectively. These findings provide new prospects for therapeutic manipulation in inflammatory diseases and cancer.
A surprising link between innate immunity and nuclear reprogramming is reported by Lee et al.; this discovery may boost the efficiency of stem cell production.
No abstract is provided for this article.
Crohn's disease is an inflammatory condition of the gastrointestinal tract with an estimated prevalence of 0.1% of the population in Western countries. Current therapies are far from ideal, relying mainly on steroids and sulfasalazine, although more recently some success has been reported in the use of agents that limit the action of tumour necrosis factor. The disease is thought to result from an interaction between environmental factors (including bacterial flora in the gut) and a genetic predisposition.
Conference Article| February 01 1996 Inhibition of NFkappaB activity by oxidative processes in intact cells — mechanism of action of pyrolidine dithiocarbamate and diamide P. Brennan; P. Brennan 1Biochemistry Department and 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 1Biochemistry Department and Biotechnology Institute, Trinity College, Dublin 2, Ireland. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1996) 24 (1): 3S. https://doi.org/10.1042/bst024003s 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 P. Brennan, L. A. J. O'neill; Inhibition of NFkappaB activity by oxidative processes in intact cells — mechanism of action of pyrolidine dithiocarbamate and diamide. Biochem Soc Trans 1 February 1996; 24 (1): 3S. doi: https://doi.org/10.1042/bst024003s 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 Keywords: NFκB, Nuclear factor κB, ILI, Interleukin 1, PDTC, pyrolidine dithiocarbamate, TNF, Tumor necrosis factor This content is only available as a PDF. © 1996 Biochemical Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.
Finding matched donors to provide bone marrow for the treatment of leukemia is not always easy, particularly if you are an African-American. Three out of five of those requiring a donor fail to find one, compared with only one in ten Caucasians who fail to find a donor. The use of umbilical cord blood, a very rich source of progenitor and stem cells, and thus, a viable alternative to bone marrow, is being strongly advocated by several centers in the USA. A federally funded program for collecting cord blood has recently begun in these centers. It took the National Marrow Donor Program ten years to build up a pool of four million individuals who are typed for potential bone-marrow donation; there are four million births per year in the USA, each a potential opportunity to collect cord blood. The use of cord blood has many other advantages, including a much lower probability of causing graft-versus-host disease, where donor immune cells reject the recipient tissue. The storage of cord blood is therefore proceeding rapidly, and the availability of such stores will greatly speed up the matching of donors and recipients. Several companies are also offering to store a baby's cord blood for potential future use. However, the costs can be significant (an average of $1 500 for collection and $95 per year for storage) and the likelihood of an individual ever needing this blood to treat their own leukemia is slight, standing at a 1 in 200 000 chance, according to the NIH. Nevertheless, as the list of diseases that might respond to stem-cell therapy expands (e.g. heart disease, see ‘Fixing a broken heart with bone’), perhaps the storage of your own cord blood might not be such a bad idea. LON
Background:The Inflammasomes are multi-protein complexes that regulate caspase-1 activation and the production of the pro-inflammatory cytokine IL-1b.Previous studies identified a class of diarylsulfonylurea containing compounds called Cytokine Release Inhibitory Drugs (CRIDs) that inhibited the post-translational processing of IL-1b.Further work identified Glutathione S-Transferase Omega 1 (GSTO1) as a possible target of these CRIDs.This study aimed to investigate the mechanism of the inhibitory activity of the CRID CP-456,773 (termed CRID3) in light of recent advances in the area of inflammasome activation, and to clarify the potential role of GSTO1 in the regulation of IL-1b production. Methodology and Results:In murine bone marrow derived macrophages, CRID3 inhibited IL-1b secretion and caspase 1 processing in response to stimulation of NLRP3 and AIM2 but not NLRC4.CRID3 also prevented AIM2 dependent pyroptosis in contrast to the NLRP3 inhibitors glyburide and parthenolide, which do not inhibit AIM2 activation.Confocal microscopy and Western blotting assays indicated that CRID3 inhibited the formation of ASC complexes or 'specks' in response to NLRP3 and AIM2 stimulation.Co-immunoprecipitation assays show that GSTO1 interacted with ASC.Significance: These results identify CRID3 as a novel inhibitor of the NLRP3 and AIM2 inflammasomes and provide an insight into the mechanism of action of this small molecule.In addition GSTO1 may be a component of the inflammasome that is required for ASC complex formation.
序、生命とは何か—それからの五〇年 二〇世紀の生物学のうち何が生き残るだろうか 『生命とは何か』—歴史上の問題として 人間の創造性の進化 発生：卵は計算可能か、あるいは私たちが天使や恐竜を生み出すことができるか 言語と生命 タンパク質なしのＲＮＡあるいはＲＮＡなしのタンパク質？ 『生命とは何か』—シュレーディンガーは果たして正しかったか 心を理解するためになぜ新しい物理が必要か 自然の法則は進化するか？ 生体において期待される新しい法則—脳と行動のシナジェティクス 無秩序から秩序へ—生物学における複雑系の熱力学 回想
