DOCSLIB.ORG

The Role of Interleukin-18 in the Metabolic Syndrome Marius Trøseid1*, Ingebjørg Seljeflot1,2, Harald Arnesen1,2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of Interleukin-18 in the Metabolic Syndrome Marius Trøseid1*, Ingebjørg Seljeflot1,2, Harald Arnesen1,2 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Trøseid et al. Cardiovascular Diabetology 2010, 9:11 CARDIO http://www.cardiab.com/content/9/1/11 VASCULAR DIABETOLOGY REVIEW Open Access The role of interleukin-18 in the metabolic syndrome Marius Trøseid1*, Ingebjørg Seljeflot1,2, Harald Arnesen1,2 Abstract The metabolic syndrome is thought to be associated with a chronic low-grade inflammation, and a growing body of evidence suggests that interleukin-18 (IL-18) might be closely related to the metabolic syndrome and its conse- quences. Circulating levels of IL-18 have been reported to be elevated in subjects with the metabolic syndrome, to be closely associated with the components of the syndrome, to predict cardiovascular events and mortality in populations with the metabolic syndrome and to precede the development of type 2 diabetes. IL-18 is found in the unstable atherosclerotic plaque, in adipose tissue and in muscle tissue, and is subject to several regulatory steps including cleavage by caspase-1, inactivation by IL-18 binding protein and the influence of other cytokines in modulating its interaction with the IL-18 receptor. The purpose of this review is to outline the role of IL-18 in the metabolic syndrome, with particular emphasis on cardiovascular risk and the potential effect of life style interventions. Introduction developing CVD is approximately doubled in the meta- The metabolic syndrome is a cluster of risk factors that bolic syndrome [10]. In a meta-analysis including identifies a population with increased risk for developing 43 cohorts, the relative risk for cardiovascular events type 2 diabetes mellitus and cardiovascular disease and death was 1.78, with the highest risk in women [11]. (CVD). The syndrome has received increased attention There is increasing evidence that the metabolic syn- after practical definitions by the Adult Treatment Panel drome is associated with a chronic, low-grade inflamma- III and International Diabetes Federation [1,2]. The tion [2]. Several pro-inflammatory cytokines have been diagnostic criteria vary slightly, in particular concerning shown to be elevated in parallel with an increasing the meausure for central obesity, but in a recent state- number of components of the syndrome, whereas the ment it is agreed that the presence of any three of the anti-inflammatory and adipocyte-specific substance adi- following five components is diagnostic for the meta- ponectin is consistently lower [12-15]. Some investiga- bolic syndrome: Central obesity, elevated blood pressure, tors have discussed that both type 2 diabetes, metabolic raised fasting glucose, raised levels of trigycerides and syndrome and atherosclerosis are multifactorial condi- low levels of high-density lipoprotein cholesterol [3]. tions which appear to have a common inflammatory More than 25% of the US population can be classified basis [16], and it is currently discussed if a measure of as having the metabolic syndrome, and the prevalence is inflammation should be included in the definition of the increasing with age, affecting >40% of US adults above syndrome [2,17]. So far, CRP has been the most likely the age of 60 years [4-6]. candidate [17,18]. The metabolic syndrome is a strong predictor of type However, a growing body of evidence suggests that IL- 2 diabetes, with an increased incidence rate of 5 to 18 is closely associated with the metabolic syndrome and 7-fold [7,8]. Indeed, the increased cardiovascular risk its consequences. The purpose of this review is to outline might develop as a continuum in parallel with increasing the role of IL-18 in the metabolic syndrome, with parti- fasting glucose, from the normal range via impaired fast- cular emphasis on CVD risk and life style interventions. ing glucose to overt diabetes mellitus [9]. The risk of Interleukin-18: a unique proinflammatory cytokine * Correspondence: [email protected] IL-18 is a member of the IL-1 family of cytokines and 1Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway was originally described as an interferon gamma (IFN-g) © 2010 Trøseid et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Trøseid et al. Cardiovascular Diabetology 2010, 9:11 Page 2 of 8 http://www.cardiab.com/content/9/1/11 inducing factor [19]. The cytokine is produced constitu- levels of IL-18, impaired insulin sensitivity and increased tively in many different cell types, including macro- risk of having the metabolic syndrome [45], suggesting phages, endothelial cells, vascular smooth muscle cells, that IL-18 might be involved in the pathogenesis of the dendritic cells and Kupffer cells [20-22]. IL-18 is also syndrome. produced in adipocytes [23], but non-adipocyte cells Circulating levels of IL-18 have consistently been have been identified as the main source of IL-18 in adi- reported to be elevated in patients with type 2 diabetes pose tissue [24]. In contrast to most other cytokines, mellitus in cross sectional studies [40,46,47], and have but in a similar way to IL-1b, IL-18 is expressed as a also been suggested to contribute to microangiopathy precursor, pro-IL18, which is inactive until cleaved by such as nephropathy in type 2 diabetes [48]. Moreover, the enzyme caspase-1 [25]. Notably, caspase-1 itself in two prospective cohorts, elevated levels of IL-18 have exists as an inactive precursor which requires the assem- been shown to predict the development of type 2 dia- bly of multi-unit complexes, known as inflammasomes, betes (Table 1) [49,50]. However, a major limitation of to be activated [26,27]. both studies is that fasting glucose or oral glucose toler- Once secreted, IL-18 is bound and inactivated by IL- ance tests were not performed at baseline evaluation: 18 binding protein, which is enhanced as a negative Elevated fasting glucose increases the risk of diabetes, feedback mechanism in response to increased IL-18 pro- and experimental hyperglycemia might increase circulat- duction, ensuring protection from tissue damage due to ing levels of IL-18 [51]. uncontrolled proinflammatory activity [28,29]. IL-18 binds to its receptor, consisting of an a chain which is Interleukin-18 and cardiovascular disease responsible for extracellular binding of IL-18, and a b Studies regarding assocations between IL-18 and stable chain which is responsible for intracellular signal trans- atherosclerosis have yielded conflicting results. One duction [25,30,31]. Although both free and protein- study showed that elevated levels of IL-18 were asso- bound IL-18 may bind to the a chain, only the free frac- ciated with the presence of subclinical atherosclerosis tion is able to activate the b chain [28,29]. evaluated with intima media thickness of the carotid IL-18 is a potent proinflammatory cytokine which artery, also after adjustment for traditional risk factors, enhances T cell and natural killer cell maturation, as CRP and IL-6 [52]. On the other hand, in two large stu- well as the production of cytokines, chemokines and cell dies elevated levels of IL-18 were associated with carotid adhesion molecules [32,33]. Of note, in CD4+ lympho- intima media thickness in univariate analyses, but not cytes IL-18 can stimulate both type 1 helper T (Th1) after adjustment for traditional risk factors [38,53]. and Th2 responses depending on its cytokine milieu: IL- Furthermore, in a study of patients with type 2 diabetes, 18 may stimulate a Th2 response in combination with both carotid intima media thickness and brachial-ankle IL-2, and may act synergistically with IL-12 to stimulate pulse wave velocity were significantly associated with a Th1 response with production of IFN-g [25], a central serum levels of IL-18, although not in multivariate ana- feature in the atherosclerotic lesion (Figure 1). One lyses [54]. However, we recently showed that arterial mechanism underlying this synergistic effect is that IL- stiffness measured by brachial pulse wave propagation 12 may induce the a chain of the IL-18 receptor in lym- was associated with IL-18 levels and components of the phocytes [34,35], whereas in non-T cells such as macro- metabolic syndrome, even in multivariate analyses, both phages, the IL-18 receptor is constitutively expressed. cross sectionally and during three years follow up [55]. Also data regarding IL-18 as a potential predictor of Interleukin-18 in the metabolic syndrome and type 2 future cardiovascular events have so far been conflicting diabetes (Table 1). In patients with known coronary artery dis- IL-18 has in several studies been associated with obesity ease, circulating IL-18 levels as well as polymorphisms [14,36-38], insulin resistance [39-41], hypertension [42] in the IL-18 gene were associated with future cardiovas- and dyslipidemia [14,37]. Furthermore, IL-18 has been cular mortality [56,57]. In two prospective studies, ele- shown to be elevated in subjects with the metabolic syn- vated IL-18 levels were associated with future drome [43] and to increase in parallell with an increas- cardiovascular disease in previously healthy men [58] ing number of components of the syndrome [38]. In a and women [59]. However, another large population large cross sectional study, elevated IL-18 levels were based study with a follow up of 11 years showed that associated with increasing number of components also increased levels of IL-6 and CRP, but not IL-18 were after adjustment for insulin resistance, obesity, IL-6 and associated with future coronary events [60].
Load more

Recommended publications
  • DS Human IL-18
    ® MSD Human IL-18 Kit For quantitative determination in human serum, plasma, and tissue culture supernatants Alzheimer’s Disease IL-18 BioProcess Cardiac Cell Signaling Clinical Immunology Cytokines Growth Factors Hypoxia Immunogenicity Inflammation Metabolic Oncology Interleukin-18 (IL-18) is an 18 kDa cytokine and a co-stimulatory factor that is produced in Kuppfer cells, activated macrophages, Toxicology keratinocytes, and intestinal epithelial cells.1 One of the main functions of IL-18 is to promote the production of IFN-γ from T and NK Vascular cells, particularly in the presence of IL-12p70. IL-18 also promotes the secretion of other proinflammatory cytokines like TNF-α, IL-1β, 2 and GM-CSF that enhance the migration and activtion of neutrophils during microbial infections. IL-18 enhances cytotoxic activity and 2,3 Catalog Numbers proliferation of CD8+ T and NK cells and has been shown to stimulate the production of IL-13 and other Th2 cytokines. Dysregulation of IL-18 may therefore contribute to inflammatory-associated disorders, unchecked infections, autoimmune diseases such as 2,3 Human IL-18 Kit rheumatoid arthritis, acute and chronic kidney injury, cancer, and pathogenic conditions related to metabolic syndrome. Kit size The MSD Human IL - 18 assay is available on 96-well 4-spot plates. This datasheet outlines the performance of the assay. 1 plate K151MCD-1 5 plates K151MCD-2 Assay Sensitivity 25 plates K151MCD-4 IL-18 LLOD (pg/mL) 0.71 The lower limit of detection (LLOD) is a calculated concentration based on a signal Ordering information 2.5 standard deviations above the background (zero calibrator blank).
    [Show full text]
  • Role of Interleukin 36Γ in Host Defense Against Tuberculosis Fadhil Ahsan,1,2,A Pedro Moura-Alves,1,A Ute Guhlich-Bornhof,1 Marion Klemm,1 Stefan H
    The Journal of Infectious Diseases MAJOR ARTICLE Role of Interleukin 36γ in Host Defense Against Tuberculosis Fadhil Ahsan,1,2,a Pedro Moura-Alves,1,a Ute Guhlich-Bornhof,1 Marion Klemm,1 Stefan H. E. Kaufmann,1 and Jeroen Maertzdorf1 Downloaded from https://academic.oup.com/jid/article-abstract/214/3/464/2577344 by Deutsches Rheumaforschungs Zentrum user on 26 June 2019 1Department of Immunology, Max Planck Institute for Infection Biology, and 2ZIBI Graduate School Berlin, Germany Tuberculosis remains a major killer worldwide, not the least because of our incomplete knowledge of protective and pathogenic immune mechanism. The roles of the interleukin 1 (IL-1) and interleukin 18 pathways in host defense are well established, as are their regulation through the inflammasome complex. In contrast, the regulation of interleukin 36γ (IL-36γ), a recently described member of the IL-1 family, and its immunological relevance in host defense remain largely unknown. Here we show that Myco- bacterium tuberculosis infection of macrophages induces IL-36γ production in a 2-stage-regulated fashion. In the first stage, mi- crobial ligands trigger host Toll-like receptor and MyD88-dependent pathways, leading to IL-36γ secretion. In the second stage, endogenous IL-1β and interleukin 18 further amplify IL-36γ synthesis. The relevance of this cytokine in the control of M. tuber- culosis is demonstrated by IL-36γ–induced antimicrobial peptides and IL-36 receptor–dependent restriction of M. tuberculosis growth. Thus, we provide first insight into the induction and regulation of the proinflammatory cytokine IL-36γ during tuberculosis. Keywords. IL-36γ; Mycobacterium tuberculosis; TLR; inflammasome; antimicrobial peptide.
    [Show full text]
  • IL-33 Can Promote Survival, Adhesion and Cytokine Production in Human
    Laboratory Investigation (2007) 87, 971–978 & 2007 USCAP, Inc All rights reserved 0023-6837/07 $30.00 IL-33 can promote survival, adhesion and cytokine production in human mast cells Motoyasu Iikura1,2, Hajime Suto1,3, Naoki Kajiwara4, Keisuke Oboki5, Tatsukuni Ohno5, Yoshimichi Okayama4, Hirohisa Saito3,5, Stephen J Galli1 and Susumu Nakae1,3,5 IL-33 is a recently identified member of the IL-1 family of molecules, which also includes IL-1 and IL-18. IL-33 binds to the receptor, T1/ST2/IL-1R4, and can promote cytokine secretion by Th2 cells and NF-kB phosphorylation in mouse mast cells. However, the effects of these molecules, especially IL-33, in human mast cells are poorly understood. Expression of the receptors for IL-1 family molecules, specifically, IL-1R1, IL-18R and T1/ST2, was detectable intracellularly in human umbilical cord blood-derived mast cells (HUCBMCs) by flow cytometry, but was scarcely detectable on the cells’ surface. However, IL-1b, IL-18 or IL-33 induced phosphorylation of Erk, p38 and JNK in naı¨ve HUCBMCs, and IL-33 or IL-1b, but not IL-18, enhanced the survival of naive HUCBMCs and promoted their adhesion to fibronectin. IL-33 or IL-1b also induced IL-8 and IL-13 production in naı¨ve HUCBMCs, and enhanced production of these cytokines in IgE/anti-IgE-stimulated HUCBMCs, without enhancing secretion of either PGD2 or histamine. Moreover, IL-33-mediated IL-8 production by HUCBMCs was markedly reduced by the p38 MAPK inhibitor, SB203580. In contrast to findings with mouse mast cells, IL-18 neither induced nor enhanced secretion of the mediators PGD2 or histamine by HUCBMCs.
    [Show full text]
  • Interleukin-18 in Health and Disease
    International Journal of Molecular Sciences Review Interleukin-18 in Health and Disease Koubun Yasuda 1 , Kenji Nakanishi 1,* and Hiroko Tsutsui 2 1 Department of Immunology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan; [email protected] 2 Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-798-45-6573 Received: 21 December 2018; Accepted: 29 January 2019; Published: 2 February 2019 Abstract: Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 receptor (IL-18R) expressing Th1 cells, which increase IFN-γ production in response to IL-18 stimulation. Therefore, IL-12 is a commitment factor that induces the development of Th1 cells. In contrast, IL-18 is a proinflammatory cytokine that facilitates type 1 responses. However, IL-18 without IL-12 but with IL-2, stimulates NK cells, CD4+ NKT cells, and established Th1 cells, to produce IL-3, IL-9, and IL-13. Furthermore, together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Therefore, IL-18 is a cytokine that stimulates various cell types and has pleiotropic functions. IL-18 is a member of the IL-1 family of cytokines. IL-18 demonstrates a unique function by binding to a specific receptor expressed on various types of cells.
    [Show full text]
  • Comprehensive Association Study of Genetic Variants in the IL-1 Gene Family in Systemic Juvenile Idiopathic Arthritis
    Genes and Immunity (2008) 9, 349–357 & 2008 Nature Publishing Group All rights reserved 1466-4879/08 $30.00 www.nature.com/gene ORIGINAL ARTICLE Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis CJW Stock1, EM Ogilvie1, JM Samuel1, M Fife1, CM Lewis2 and P Woo1 1Centre for Paediatric and Adolescent Rheumatology, Windeyer Institute for Medical Sciences, University College London, London, UK and 2Guy’s, Kings and St Thomas’ School of Medicine, London, UK Patients with systemic juvenile idiopathic arthritis (sJIA) have a characteristic daily spiking fever and elevated levels of inflammatory cytokines. Members of the interleukin-1 (IL-1) gene family have been implicated in various inflammatory and autoimmune diseases, and treatment with the IL-1 receptor antagonist, Anakinra, shows remarkable improvement in some patients. This work describes the most comprehensive investigation to date of the involvement of the IL-1 gene family in sJIA. A two-stage case–control association study was performed to investigate the two clusters of IL-1 family genes using a tagging single nucleotide polymorphism (SNP) approach. Genotyping data of 130 sJIA patients and 151 controls from stage 1 highlighted eight SNPs in the IL1 ligand cluster region and two SNPs in the IL1 receptor cluster region as showing a significant frequency difference between the populations. These 10 SNPs were typed in an additional 105 sJIA patients and 184 controls in stage 2. Meta-analysis of the genotypes from both stages showed that three IL1 ligand cluster SNPs (rs6712572, rs2071374 and rs1688075) and one IL1 receptor cluster SNP (rs12712122) show evidence of significant association with sJIA.
    [Show full text]
  • Evolutionary Divergence and Functions of the Human Interleukin (IL) Gene Family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W
    UPDATE ON GENE COMPLETIONS AND ANNOTATIONS Evolutionary divergence and functions of the human interleukin (IL) gene family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W. Nebert3* and Vasilis Vasiliou1 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected]; [email protected] Date received (in revised form): 22nd September 2010 Abstract Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term ‘interleukin’ (IL) has been used to describe a group of cytokines with complex immunomodulatory functions — including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host’s immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type.
    [Show full text]
  • Interleukin-18 and Interleukin-18 Receptor-A Expression in Allergic Asthma
    Interleukin-18 and interleukin-18 receptor-a expression in allergic asthma To the Editors: were centrifuged at 4056g (1,500 rpm) for 10 min at 4uC. The supernatant was aspirated and the cells were fixed with The inflammatory process in allergic asthma is initiated by T- 350 mL of 1% paraformaldehyde. Stained cells were then helper (Th) type-2 cells, which produce a repertoire of stored in the dark at 4uC until flow-cytometric acquisition cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13, ,48 h after staining. which are necessary for immunoglobulin (Ig)E production, airway eosinophilia and goblet cell hyperplasia [1]. IL-18 is Cells were acquired with a 15-colour LSR II flow cytometer another pro-inflammatory cytokine, initially described as equipped with three lasers (Becton Dickinson Instrument interferon (IFN)-c-inducing factor [2]. IL-18 can act as a Systems, Franklin Lakes, NJ, USA) using the FACSDiva cofactor for Th2 cell development and IgE production [3]. software (BD Biosciences). A lymphocyte gate was set up Recently, an IL-18 gene polymorphism was reported to be around the lymphocyte cell population on the side scatter (SSC) associated with asthma severity and higher serum IL-18 levels: versus CD45 plot and then transferred to a SSC versus CD3 plot to the rs5744247 variant, which has higher transcriptional activity identify CD3-positive and -negative cell populations. CD3- than the wildtype allele [4]. In addition, the IL-18 receptor (IL- positive cell populations were separated from CD4- and CD8- 18R) gene (on 2q21) has been identified as a candidate gene positive cell populations by CD4 versus CD8 plot.
    [Show full text]
  • Family Member in Teleost Fish Identification of a Novel IL-1 Cytokine
    Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish Tiehui Wang, Steve Bird, Antonis Koussounadis, Jason W. Holland, Allison Carrington, Jun Zou and Christopher J. This information is current as Secombes of September 25, 2021. J Immunol 2009; 183:962-974; Prepublished online 24 June 2009; doi: 10.4049/jimmunol.0802953 http://www.jimmunol.org/content/183/2/962 Downloaded from References This article cites 66 articles, 10 of which you can access for free at: http://www.jimmunol.org/content/183/2/962.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Identification of a Novel IL-1 Cytokine Family Member in Teleost Fish1 Tiehui Wang,* Steve Bird,* Antonis Koussounadis,† Jason W. Holland,* Allison Carrington,* Jun Zou,* and Christopher J. Secombes2* A novel IL-1 family member (nIL-1F) has been discovered in fish, adding a further member to this cytokine family.
    [Show full text]
  • Uniprot Nr. Proseek Panel 2,4-Dienoyl-Coa Reductase, Mitochondrial
    Protein Name (Short Name) Uniprot Nr. Proseek Panel 2,4-dienoyl-CoA reductase, mitochondrial (DECR1) Q16698 CVD II 5'-nucleotidase (5'-NT) P21589 ONC II A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAM-TS13) Q76LX8 CVD II A disintegrin and metalloproteinase with thrombospondin motifs 15 (ADAM-TS 15) Q8TE58 ONC II Adenosine Deaminase (ADA) P00813 INF I ADM (ADM) P35318 CVD II ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38) P28907 NEU I Agouti-related protein (AGRP) O00253 CVD II Alpha-2-macroglobulin receptor-associated protein (Alpha-2-MRAP) P30533 NEU I Alpha-L-iduronidase (IDUA) P35475 CVD II Alpha-taxilin (TXLNA) P40222 ONC II Aminopeptidase N (AP-N) P15144 CVD III Amphiregulin (AR) P15514 ONC II Angiopoietin-1 (ANG-1) Q15389 CVD II Angiopoietin-1 receptor (TIE2) Q02763 CVD II Angiotensin-converting enzyme 2 (ACE2) Q9BYF1 CVD II Annexin A1 (ANXA1) P04083 ONC II Artemin (ARTN) Q5T4W7 INF I Axin-1 (AXIN1) O15169 INF I Azurocidin (AZU1 P20160 CVD III BDNF/NT-3 growth factors receptor (NTRK2) Q16620 NEU I Beta-nerve growth factor (Beta-NGF) P01138 NEU I, INF I Bleomycin hydrolase (BLM hydrolase) Q13867 CVD III Bone morphogenetic protein 4 (BMP-4) P12644 NEU I Bone morphogenetic protein 6 (BMP-6) P22004 CVD II Brain-derived neurotrophic factor (BDNF) P23560 NEU I, INF I Brevican core protein (BCAN) Q96GW7 NEU I Brorin (VWC2) Q2TAL6 NEU I Brother of CDO (Protein BOC) Q9BWV1 CVD II Cadherin-3 (CDH3) P22223 NEU I Cadherin-5 (CDH5) P33151 CVD III Cadherin-6 (CDH6) P55285 NEU I Carbonic anhydrase 5A, mitochondrial
    [Show full text]
  • Supplemental Table S10. Differentially Expressed Interleukins Comparing SARS-Cov-2 Versus Medium
    Supplemental Table S10. Differentially expressed interleukins comparing SARS-CoV-2 versus medium ProbeName p ([SARS-CoV-2]Regulation Vs [Medium])FC ([SARS-CoV-2] ([SARS-CoV-2]GeneSymbol Vs Vs [Medium]) [Medium])Description A_33_P3211608 3,97E-02 up 2,974933 IL1RL1 Homo sapiens interleukin 1 receptor-like 1 (IL1RL1), transcript variant 4, non-coding RNA [NR_104167] A_23_P17053 6,39262E-05 up 6,132556 IL36G Homo sapiens interleukin 36, gamma (IL36G), transcript variant 1, mRNA [NM_019618] A_33_P3339625 1,17303E-05 up 16,473091 IL17C Homo sapiens interleukin 17C (IL17C), mRNA [NM_013278] A_33_P3243230 1,76904E-07 up 16,647413 HSINTLK8M interleukin 8 {Homo sapiens} (exp=-1; wgp=0; cg=0), partial (97%) [THC2544321] A_32_P223777 0,00139653 up 1,9878159 IL6ST Homo sapiens interleukin 6 signal transducer (IL6ST), transcript variant 1, mRNA [NM_002184] A_23_P76078 0,045698304 up 1,8592229 IL23A Homo sapiens interleukin 23, alpha subunit p19 (IL23A), mRNA [NM_016584] A_23_P336554 0,00221631 up 1,7976834 IL1RAP Homo sapiens interleukin 1 receptor accessory protein (IL1RAP), transcript variant 2, mRNA [NM_134470] A_33_P3251876 0,03411692 up 1,5917065 IL18R1 Homo sapiens interleukin 18 receptor 1 (IL18R1), transcript variant 1, mRNA [NM_003855] A_33_P3211666 0,026903022 up 1,5705488 IL18R1 Homo sapiens interleukin 18 receptor 1 (IL18R1), transcript variant 1, mRNA [NM_003855] A_23_P90925 0,004416244 up 2,695789 IL36B Homo sapiens interleukin 36, beta (IL36B), transcript variant 2, mRNA [NM_173178] A_24_P68783 0,000239245 up 2,834167 IL36RN Homo sapiens
    [Show full text]
  • Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1Β
    Cutting Edge: Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1β This information is current as Qifan Zhu and Thirumala-Devi Kanneganti of October 1, 2021. J Immunol published online 3 May 2017 http://www.jimmunol.org/content/early/2017/05/03/jimmun ol.1700352 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2017/05/03/jimmunol.170035 Material 2.DCSupplemental Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 1, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published May 3, 2017, doi:10.4049/jimmunol.1700352 Th eJournal of Cutting Edge Immunology Cutting Edge: Distinct Regulatory Mechanisms Control Proinflammatory Cytokines IL-18 and IL-1b Qifan Zhu*,† and Thirumala-Devi Kanneganti* Interleukin-18 and IL-1b, which are cytokines of the expressed in murine macrophages, dendritic cells, endothelial IL-1 family, are synthesized as precursor proteins and cells, intestinal epithelial cells, and keratinocytes under steady activated by the inflammasome via proteolytic process- state (8–10).
    [Show full text]
  • IL-18 Drives ILC3 Proliferation and Promotes IL-22 Production Via NF-Κb
    IL-18 Drives ILC3 Proliferation and Promotes IL-22 Production via NF- κB Aaron R. Victor, Ansel P. Nalin, Wenjuan Dong, Susan McClory, Min Wei, Charlene Mao, Raleigh D. Kladney, This information is current as Youssef Youssef, Wing Keung Chan, Edward L. Briercheck, of October 3, 2021. Tiffany Hughes, Steven D. Scoville, Jason R. Pitarresi, Charlie Chen, Sarah Manz, Lai-Chu Wu, Jianying Zhang, Michael C. Ostrowski, Aharon G. Freud, Gustavo W. Leone, Michael A. Caligiuri and Jianhua Yu J Immunol 2017; 199:2333-2342; Prepublished online 25 Downloaded from August 2017; doi: 10.4049/jimmunol.1601554 http://www.jimmunol.org/content/199/7/2333 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2017/08/24/jimmunol.160155 Material 4.DCSupplemental References This article cites 76 articles, 31 of which you can access for free at: http://www.jimmunol.org/content/199/7/2333.full#ref-list-1 by guest on October 3, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2017 by The American Association of Immunologists, Inc.
    [Show full text]