DOCSLIB.ORG

Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion This information is current as Carle Ryckman, Karen Vandal, Pascal Rouleau, Mariève of September 27, 2021. Talbot and Philippe A. Tessier J Immunol 2003; 170:3233-3242; ; doi: 10.4049/jimmunol.170.6.3233 http://www.jimmunol.org/content/170/6/3233 Downloaded from References This article cites 55 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/170/6/3233.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 27, 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 © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion1 Carle Ryckman, Karen Vandal, Pascal Rouleau, Marie`ve Talbot, and Philippe A. Tessier2 S100A8 and S100A9 are small calcium-binding proteins that are highly expressed in neutrophil and monocyte cytosol and are found at high levels in the extracellular milieu during inflammatory conditions. Although reports have proposed a proinflam- matory role for these proteins, their extracellular activity remains controversial. In this study, we report that S100A8, S100A9, and -S100A8/A9 caused neutrophil chemotaxis at concentrations of 10؊12–10؊9 M. S100A8, S100A9, and S100A8/A9 stimulated shed ding of L-selectin, up-regulated and activated Mac-1, and induced neutrophil adhesion to fibrinogen in vitro. Neutralization with Ab showed that this adhesion was mediated by Mac-1. Neutrophil adhesion was also associated with an increase in intracellular calcium levels. However, neutrophil activation by S100A8, S100A9, and S100A8/A9 did not induce actin polymerization. Finally, injection of S100A8, S100A9, or S100A8/A9 into a murine air pouch model led to rapid, transient accumulation of neutrophils Downloaded from confirming their activities in vivo. These studies 1) show that S100A8, S100A9, and S100A8/A9 are potent stimulators of neutro- phils and 2) strongly suggest that these proteins are involved in neutrophil migration to inflammatory sites. The Journal of Immunology, 2003, 170: 3233–3242. uring inflammatory responses, neutrophils migrate in a from infections and inflammatory pathologies. High serum con- multistep fashion (reviewed in Ref. 1) from the blood to centrations of MRPs have been found in advanced HIV infections, http://www.jimmunol.org/ D inflammatory sites where they are involved in immune adult and juvenile rheumatoid arthritis, chronic bronchitis, cystic fi- defense. First, interactions between selectins and glycans mediate brosis, systemic lupus erythematosus, and granulomatous conditions, neutrophils rolling along the endothelium. Neutrophils are then such as tuberculosis and sarcoidosis (10, 15–20). S100A8/A9 is the ␤ activated through change in 2 integrins to an active conformation. main form found in the extracellular milieu and its in vitro release by This conformational change thought to be induced by lipid medi- neutrophils, activated monocytes, and macrophages has also been ators such as platelet-activating factor or chemokines like IL-8, demonstrated (20–25). cause neutrophils to adhere strongly to the endothelium and ex- Extracellular S100A8, S100A9, and S100A8/A9 mediate regu- travasate. Once in the tissue, they follow concentration gradients latory and biological functions, including antiproliferative, antitu- of chemoattractants (such as C5a, leukotriene B4, and IL-8, or moral, antimicrobial, and antinociceptive activities (26–31). Like by guest on September 27, 2021 bacterial N-formylated peptides) toward the inflammatory site. other members of the S100 family (32–34), human MRPs and their Recent studies suggest that the myeloid-related proteins murine homologs possess proinflammatory activities. However, (MRPs)3 are involved in neutrophil migration. The MRPs S100A8 there are disparities in the activities ascribed to these proteins and S100A9 (10.6 and 13.5 kDa, respectively (2)) are calcium- pending a clear understanding of their activities in neutrophil mi- binding proteins that belong to the S100 protein family (3, 4); they gration to inflammatory sites. are expressed almost exclusively by cells of myeloid lineage. The Newton and Hogg (35) recently demonstrated that human MRPs are constitutively expressed in the cytosol of neutrophils S100A9 stimulates neutrophil adhesion to fibrinogen by activating where they comprise up to 30% of the cytosolic proteins (5). the ␤ integrin Mac-1 (CD11b/CD18). The promotion of this ad- Monocytes and differentiated macrophages in inflamed tissues also 2 express MRPs (4–9). S100A8 and S100A9 form noncovalent ho- hesion was negatively regulated by the formation of the hetero- modimers and a heterodimer (S100A8/A9) in a calcium-dependent complex with S100A8 implying that S100A8 as well as manner (10–12). S100A8/A9 do not stimulate neutrophil adhesion (35). Eue et al. Local secretion of MRPs has been detected in chronic periodon- (36) also reported that S100A8 do not enhanced monocyte adhe- tal infections (13, 14) as well as in the serum of patients suffering sion to endothelial cells. However, in contrast to the latter study, they demonstrated that not only S100A9 but also S100A8/A9 en- hanced monocyte adhesion to endothelial cells via Mac-1/ICAM-1 Infectious Diseases Research Center, Laval University Hospital Center, Sainte-Foy, interactions. These results suggest that S100A8 does not nega- Quebec, Canada tively regulate S100A9 activity by forming S100A8/A9. Received for publication April 26, 2002. Accepted for publication January 3, 2003. Studies conducted using murine MRPs demonstrated that mu- The costs of publication of this article were defrayed in part by the payment of page rine S100A8, called CP-10, is a potent chemotactic factor (activity charges. This article must therefore be hereby marked advertisement in accordance Ϫ13 Ϫ11 with 18 U.S.C. Section 1734 solely to indicate this fact. at 10 –10 M) for neutrophils (37), and induces sustained leukocyte recruitment in vivo (38, 39). Moreover, like human 1 This work was supported by a grant and a scholarship to P.A.T. from the Arthritis Society of Canada. C.R. is supported by a studentship from the K. H. Hunter Char- S100A9, murine S100A8 does not stimulate calcium flux, shed- itable Foundation and the Canadian Institutes of Health Research. ␤ ding of L-selectin, or up-regulation of the 2 integrin Mac-1 on 2 Address correspondence and reprint requests to Dr. Philippe A. Tessier, Room RC neutrophils (35, 37, 40). In contrast to its murine homolog, 709, Infectious Diseases Research Center, Laval University Hospital Center, 2705 Laurier Boulevard, Sainte-Foy, Quebec, Canada G1V 4G2. E-mail address: human S100A8 is supposedly not chemotactic for neutrophils, [email protected] but has been reported to be chemotactic for periodontal liga- 3 Abbreviation used in this paper: MRP, myeloid-related protein. ment cells (35, 41). Copyright © 2003 by The American Association of Immunologists, Inc. 0022-1767/03/$02.00 3234 PROINFLAMMATORY ACTIVITIES OF S100A8, S100A9, AND S100A8/A9 Therefore, the exact activities of S100A8 and S100A8/A9, par- IFA, and final boost was given on day 28 with proteins alone. On day 31, ticularly their effects on neutrophil migration, remain unknown. spleen cells from the immunized mice were fused with SP2 murine my- Harrison et al. (42) showed that murine S100A8 chemotactic ac- eloma cells and cultured in hypoxanthine/amethopterin/thymidine selection medium. Culture supernatants of the hybridomas were screened by ELISA tivity can be efficiently inhibited by oxidation of the protein, dem- using plates coated with 1 ␮g/ml recombinant proteins in 0.1 M carbonate onstrating a certain susceptibility of S100A8 to inactivation. buffer (pH 9.6). Positive hybridoma cells were cloned by limiting dilution. S100A9 activity appeared to be differently affected by oxidation The mAb clones KVC/3E2 and KVC/2B9 showed the most distinctive (42). Therefore, the discrepancies in MRP activity could be due to recognition of the recombinant proteins S100A8 and S100A9, respectively. Both clones were isotyped as IgG1 kappa. Specificity of the mAbs was differences in protein activity arising from interlaboratory variation confirmed by ELISA and Western blot analysis. in purification protocols or methodologies. In this study, a different and gentle approach was used for the Neutrophil purification production and purification of the human S100A8, S100A9, and Peripheral blood was collected in heparinized tubes from healthy adult S100A8/A9 proteins. Recombinant proteins were generated and volunteers. Neutrophils were isolated as previously described by Boyum (44) and resuspended in HBSS-H (HBSS
Load more

Recommended publications
  • Datasheet: VMA00595 Product Details
    Datasheet: VMA00595 Description: MOUSE ANTI S100A8 Specificity: S100A8 Format: Purified Product Type: PrecisionAb™ Monoclonal Isotype: IgG2b Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Species Cross Reacts with: Mouse Reactivity N.B. Antibody reactivity and working conditions may vary between species. Product Form Purified IgG - liquid Preparation Mouse monoclonal antibody affinity purified on immunogen from tissue culture supernatant Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN3) Stabilisers 1% Bovine Serum Albumin Immunogen Full length recombinant human S100A8 External Database Links UniProt: P05109 Related reagents Entrez Gene: 6279 S100A8 Related reagents Synonyms CAGA, CFAG, MRP8 Page 1 of 2 Specificity Mouse anti Human S100A8 antibody recognizes S100A8, also known as MRP-8, S100 calcium- binding protein A8 (calgranulin A), calprotectin L1L subunit, leukocyte L1 complex light chain or migration inhibitory factor-related protein 8. The protein encoded by S100A8 is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs.
    [Show full text]
  • A Novel Computational Algorithm for Predicting Immune Cell Types Using Single-Cell RNA Sequencing Data
    A novel computational algorithm for predicting immune cell types using single-cell RNA sequencing data By Shuo Jia A hesis submitted to the Faculty of Graduate Studies of The University of Manitoba n partial fulfillment of the requirements of the degree of MASTER OF SCIENCE Department of Biochemistry and Medical Genetics University of Manitoba Winnipeg, Manitoba, Canada Copyright © 2020 by Shuo Jia Abstract Background: Cells from our immune system detect and kill pathogens to protect our body against many diseases. However, current methods for determining cell types have some major limitations, such as being time-consuming and with low throughput rate, etc. These problems stack up and hinder the deep exploration of cellular heterogeneity. Immune cells that are associated with cancer tissues play a critical role in revealing the stages of tumor development. Identifying the immune composition within tumor microenvironments in a timely manner will be helpful to improve clinical prognosis and therapeutic management for cancer. Single-cell RNA sequencing (scRNA-seq), an RNA sequencing (RNA-seq) technique that focuses on a single cell level, has provided us with the ability to conduct cell type classification. Although unsupervised clustering approaches are the major methods for analyzing scRNA-seq datasets, their results vary among studies with different input parameters and sizes. However, in supervised machine learning methods, information loss and low prediction accuracy are the key limitations. Methods and Results: Genes in the human genome align to chromosomes in a particular order. Hence, we hypothesize incorporating this information into our model will potentially improve the cell type classification performance. In order to utilize gene positional information, we introduce chromosome-based neural network, namely ChrNet, a novel chromosome-specific re-trainable supervised learning method based on a one-dimensional 1 convolutional neural network (1D-CNN).
    [Show full text]
  • Tumor-Infiltrating Monocytes/Macrophages Promote Tumor Invasion and Migration by Upregulating S100A8 and S100A9 Expression in Ca
    OPEN Oncogene (2016) 35, 5735–5745 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0950-9232/16 www.nature.com/onc ORIGINAL ARTICLE Tumor-infiltrating monocytes/macrophages promote tumor invasion and migration by upregulating S100A8 and S100A9 expression in cancer cells SY Lim, AE Yuzhalin, AN Gordon-Weeks and RJ Muschel Myeloid cells promote the development of distant metastases, but little is known about the molecular mechanisms underlying this process. Here we have begun to uncover the effects of myeloid cells on cancer cells in a mouse model of liver metastasis. Monocytes/macrophages, but not granulocytes, isolated from experimental liver metastases stimulated migration and invasion of MC38 colon and Lewis lung carcinoma cells. In response to conditioned media from tumor-infiltrating monocytes/macrophages, cancer cells upregulated S100a8 and S100a9 messenger RNA expression through an extracellular signal-related kinase-dependent mechanism. Suppression of S100A8 and S100A9 in cancer cells using short hairpin RNA significantly diminished migration and invasion in culture. Downregulation of S100A8 and S100A9 had no effect on subcutaneous tumor growth. However, colony size was greatly reduced in liver metastases with decreased invasion into adjacent tissue. In tissue culture and in the liver colonies derived from cancer cells with knockdown of S100A8 and S100A9, MMP2 and MMP9 expression was decreased, consistent with the reduction in migration and invasion. Our findings demonstrate that monocytes/macrophages in the metastatic liver microenvironment induce S100A8 and S100A9 in cancer cells, and that these proteins are essential for tumor cell migration and invasion. S100A8 and S100A9, however, are not responsible for stimulation of proliferation.
    [Show full text]
  • Calprotectin Poster
    70th AACC Annual Scientific Meeting & Clinical Lab Expo July 29 – August 2, 2018, Chicago, Illinois, USA Calprotectin Antibodies With Different Binding Specificities Can Be Used as Tools to Detect Multiple Calprotectin Forms 1 Laura-Leena Kiiskinen1, Sari Tiitinen 1Medix Biochemica, Klovinpellontie 3, FI-02180 Espoo, Finland Calprotectin –A Pro-Inflammatory Protein Materials & Methods Calprotectin (leucocyte L1-protein) We have developed five mouse monoclonal antibodies (mAbs) is a pro-inflammatory protein against human calprotectin: 3403 (#100460), 3404 (#100468), primarily secreted by neutrophils, 3405 (#100469), 3406 (#100470) and 3407 (#100618). Binding macrophages and monocytes at the specificities of the antibodies were studied in fluorescent site of inflammation1–4. Neutrophils immunoassays (FIA) using purified recombinant monomeric accumulate in mucosa, where calprotectin subunits S100A8 (#710018; Medix Biochemica) calprotectin is released and easily and S100A9 (#710019; Medix Biochemica), and the S100A8/A9 detectable4. complex (#610061; Medix Biochemica) as antigens. Calprotectin is comprised of two Antigens were coated onto a microtiter plate (#473709; NUNC®) calcium-binding monomers, a at 50 ng/well, blocked for 1h at room temperature, and 93-amino-acid S100A8 (MRP-8) and antibodies added at concentrations 31–1,000 ng/mL. Bound a 114-amino-acid S100A9 (MRP-14). antibodies were detected using an europium (Eu)-labeled Dimers pair non-covalently with each DELFIA® Eu-N1 Rabbit Anti-Mouse IgG antibody (#AD0207; other, forming heterotetramers. S100A8 PerkinElmer) as described previously9. and S100A9 both contain two EF-hand The specificities of calprotectin antibody pairs were studied in type Ca2+ binding sites (Figure 1). sandwich FIA. Capture antibodies (150 ng/well) were incubated Elevated serum or fecal calprotectin with the S100A8/A9 complex at concentrations 0.15–1,000 levels are indicative of several ng/mL.
    [Show full text]
  • Epidermal Ablation of Dlx3 Is Linked to IL-17–Associated Skin Inflammation
    Epidermal ablation of Dlx3 is linked to IL-17–associated skin inflammation Joonsung Hwanga,1, Ryosuke Kitaa, Hyouk-Soo Kwonb,2, Eung Ho Choic, Seung Hun Leed, Mark C. Udeyb, and Maria I. Morassoa,3 aDevelopmental Skin Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892; bDermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; cDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 220-701, Korea; and dDepartment of Dermatology, Yonsei University College of Medicine, Seoul 135-720, Korea Edited* by William E. Paul, National Institutes of Health, Bethesda, MD, and approved May 24, 2011 (received for review December 29, 2010) In an effort to understand the role of Distal-less 3 (Dlx3) in cutane- Distal-less 3 (Dlx3) is a homeobox transcription factor involved ous biology and pathophysiology, we generated and characterized in terminal differentiation of keratinocytes (12). Misexpression of a mouse model with epidermal ablation of Dlx3. K14cre;Dlx3Kin/f Dlx3 in the basal layer results in decreased keratinocyte pro- mice exhibited epidermal hyperproliferation and abnormal differ- liferation and premature terminal differentiation (13). To study entiation of keratinocytes. Results from subsequent analyses the role of Dlx3 in the skin homeostasis, we generated conditional revealed cutaneous inflammation that featured accumulation of epidermis-specific knockout K14cre;Dlx3Kin/f mice (14). In the IL-17–producing CD4+ T, CD8+ T, and γδ T cells in the skin and lymph present study, we characterized the abnormal differentiation and nodes of K14cre;Dlx3Kin/f mice.
    [Show full text]
  • Calprotectin: an Ignored Biomarker of Neutrophilia in Pediatric Respiratory Diseases
    children Review Calprotectin: An Ignored Biomarker of Neutrophilia in Pediatric Respiratory Diseases Grigorios Chatziparasidis 1 and Ahmad Kantar 2,* 1 Primary Cilia Dyskinesia Unit, School of Medicine, University of Thessaly, 41110 Thessaly, Greece; [email protected] 2 Pediatric Asthma and Cough Centre, Instituti Ospedalieri Bergamaschi, University and Research Hospitals, 24046 Bergamo, Italy * Correspondence: [email protected] Abstract: Calprotectin (CP) is a non-covalent heterodimer formed by the subunits S100A8 (A8) and S100A9 (A9). When neutrophils become activated, undergo disruption, or die, this abundant cytosolic neutrophil protein is released. By fervently chelating trace metal ions that are essential for bacterial development, CP plays an important role in human innate immunity. It also serves as an alarmin by controlling the inflammatory response after it is released. Extracellular concentrations of CP increase in response to infection and inflammation, and are used as a biomarker of neutrophil activation in a variety of inflammatory diseases. Although it has been almost 40 years since CP was discovered, its use in daily pediatric practice is still limited. Current evidence suggests that CP could be used as a biomarker in a variety of pediatric respiratory diseases, and could become a valuable key factor in promoting diagnostic and therapeutic capacity. The aim of this study is to re-introduce CP to the medical community and to emphasize its potential role with the hope of integrating it as a useful adjunct, in the practice of pediatric respiratory medicine. Citation: Chatziparasidis, G.; Kantar, Keywords: calprotectin; S100A8/A9; children; lung A. Calprotectin: An Ignored Biomarker of Neutrophilia in Pediatric Respiratory Diseases. Children 2021, 8, 428.
    [Show full text]
  • Integrated DNA Methylation and Gene Expression Analysis Identi Ed
    Integrated DNA methylation and gene expression analysis identied S100A8 and S100A9 in the pathogenesis of obesity Ningyuan Chen ( [email protected] ) Guangxi Medical University https://orcid.org/0000-0001-5004-6603 Liu Miao Liu Zhou People's Hospital Wei Lin Jiangbin Hospital Dong-Hua Zhou Fifth Aliated Hospital of Guangxi Medical University Ling Huang Guangxi Medical University Jia Huang Guangxi Medical University Wan-Xin Shi Guangxi Medical University Li-Lin Li Guangxi Medical University Yu-Xing Luo Guangxi Medical University Hao Liang Guangxi Medical University Shang-Ling Pan Guangxi Medical University Jun-Hua Peng Guangxi Medical University Research article Keywords: Obesity, DNA methylation-mRNA expression-CAD interaction network, Function enrichment, Correlation analyses Posted Date: November 2nd, 2020 Page 1/21 DOI: https://doi.org/10.21203/rs.3.rs-68833/v2 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/21 Abstract Background: To explore the association of DNA methylation and gene expression in the pathology of obesity. Methods: (1) Genomic DNA methylation and mRNA expression prole of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects; (2) functional enrichment analysis and construction of differential methylation gene regulatory network were performed; (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray data set; and (4) correlation analysis was performed on DNA methylation and mRNA expression data. Results: A total of 77 differentially expressed mRNA matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes-s100a8- cg09174555 and s100a9-cg03165378.
    [Show full text]
  • RNA Double-Stranded Monocytes
    IL-10-Dependent S100A8 Gene Induction in Monocytes/Macrophages by Double-Stranded RNA This information is current as Yasumi Endoh, Yuen Ming Chung, Ian A. Clark, Carolyn L. of September 27, 2021. Geczy and Kenneth Hsu J Immunol 2009; 182:2258-2268; ; doi: 10.4049/jimmunol.0802683 http://www.jimmunol.org/content/182/4/2258 Downloaded from References This article cites 73 articles, 26 of which you can access for free at: http://www.jimmunol.org/content/182/4/2258.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 27, 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 IL-10-Dependent S100A8 Gene Induction in Monocytes/Macrophages by Double-Stranded RNA1 Yasumi Endoh,* Yuen Ming Chung,* Ian A. Clark,† Carolyn L. Geczy,* and Kenneth Hsu2* The S100 calcium-binding proteins S100A8 and S100A9 are elevated systemically in patients with viral infections.
    [Show full text]
  • Mouse Embryo S100A8 Causes Early Resorption of the Inflammation
    A Null Mutation in the Inflammation-Associated S100 Protein S100A8 Causes Early Resorption of the Mouse Embryo This information is current as of September 25, 2021. Robert J. Passey, Elizabeth Williams, Agnieszka M. Lichanska, Christine Wells, Shengping Hu, Carolyn L. Geczy, Melissa H. Little and David A. Hume J Immunol 1999; 163:2209-2216; ; http://www.jimmunol.org/content/163/4/2209 Downloaded from 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 September 25, 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 © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. A Null Mutation in the Inflammation-Associated S100 Protein S100A8 Causes Early Resorption of the Mouse Embryo1 Robert J. Passey,* Elizabeth Williams,† Agnieszka M. Lichanska,† Christine Wells,† Shengping Hu,* Carolyn L. Geczy,* Melissa H. Little,† and David A. Hume2† S100A8 (also known as CP10 or MRP8) was the first member of the S100 family of calcium-binding proteins shown to be chemotactic for myeloid cells.
    [Show full text]
  • Zinc Deficiency Activates S100A8 Inflammation in the Absence Of
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central IJC International Journal of Cancer Zinc deficiency activates S100A8 inflammation in the absence of COX-2 and promotes murine oral-esophageal tumor progression Shao-Gui Wan1*, Cristian Taccioli2*, Yubao Jiang1, Hongping Chen1, Karl J. Smalley3, Kun Huang4, Xiu-Ping Liu2, John L. Farber5, Carlo M. Croce2 and Louise Y. Y. Fong1 1 Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 2 Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, OH 3 Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 4 Department of Biomedical Informatics, The Ohio State University, Columbus, OH 5 Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA Zinc (Zn)-deficiency (ZD) is implicated in the pathogenesis of human oral-esophageal cancers. Previously, we showed that in ZD mice genetic deletion of cyclooxygenase-2 (Cox-2) enhances N-nitrosomethylbenzylamine-induced forestomach carcinogenesis. By contrast, Cox-2 deletion offers protection in Zn-sufficient (ZS) mice. We hypothesize that ZD activates pathways insensitive to COX-2 inhibition, thereby promoting carcinogenesis. This hypothesis is tested in a Cox-22/2 mouse tongue cancer model that mimics pharmacologic blockade of COX-2 by firstly examining transcriptome profiles of forestomach mucosa from Cox-22/2 and wild-type mice on a ZD vs. ZS diet, and secondly investigating the roles of identified markers in mouse forestomach/tongue preneoplasia and carcinomas. In Cox-22/2 mice exposed to the tongue carcinogen 4-nitroquinoline 1-oxide, dietary ZD elicited tongue/esophagus/forestomach carcinomas that were prevented by ZS.
    [Show full text]
  • Integrated Bioinformatics Approach to Understand Immune-Related Key
    Integrated bioinformatics approach to understand immune-related key genes and pathways in chronic spontaneous urticaria wenxing su Second Aliated Hospital of Soochow University biao huang First Aliated Hospital of Soochow University ying zhao Second Aliated Hospital of Soochow University xiaoyan zhang Second Aliated Hospital of Soochow University lu chen second aliated hospital of soochow university jiang ji ( [email protected] ) Second Aliated Hospital of Soochow University qingqing Jiao rst aliated hospital of soochow university Research Keywords: Chronic spontaneous urticaria, bioinformatical analysis, differentially expressed genes, immune inltration Posted Date: December 31st, 2020 DOI: https://doi.org/10.21203/rs.3.rs-137346/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/29 Abstract Background Chronic spontaneous urticaria (CSU) refers to recurrent urticaria that lasts for more than 6 weeks in the absence of an identiable trigger. Due to its recurrent wheal and severe itching, CSU seriously affects patients' life quality. There is currently no radical cure for it and its vague pathogenesis limits the development of targeted therapy. With the goal of revealing the underlying mechanism, two data sets with accession numbers GSE57178 and GSE72540 were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the differentially expressed genes (DEGs) of CSU skin lesion samples and healthy controls, four kinds of analyses were performed, namely functional annotation, protein- protein interaction (PPI) network and module construction, co-expression and drug-gene interaction prediction analysis, and immune and stromal cells deconvolution analyses. Results 92 up-regulated genes and 7 down-regulated genes were selected for subsequent analyses.
    [Show full text]
  • Human S100A8 and S100A9 Scavenge Pro-Inflammatory Hypohalous Acids in Disease
    Human S100A8 and S100A9 Scavenge Pro-inflammatory Hypohalous Acids in Disease by Lincoln Henry Gomes A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy Faculty of Medicine The University of New South Wales 2012 THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: Gomes First name: Lincoln Other name/s: Henry Abbreviation for degree as given in the University calendar: PhD School: Medical Sciences Faculty: Medicine Title: S100A8 and S100A9 scavenge pro-inflammatory hypohalous acids in disease Abstract 350 words maximum: (PLEASE TYPE) S100A8, S100A9 and S100A12 are generally considered pro-inflammatory proteins because their expression is elevated in chronic inflammatory disorders. Hypohalous acids generated by activated phagocytes are scavenged by murine S100A8 and S100A9, suggesting a protective role in oxidative stress, but effects on human recombinant S100A8 and S100A9 are undefined. Hypohalous acids at low molar ratios (1:1) promoted structural changes in human S100A8 and S100A9 in vitro, generating two novel post- translational modifications on Cys42 in S100A8, defined as oxathiazolidine-oxide and dioxide. Particular methionine residues in S100A9 were also modified. S100A8 and S100A9 are increased in respiratory diseases in which reactive oxygen species are implicated and anti-oxidant mechanisms compromised. Oxidized S100A8 (oxS100A8) was prominent in asthmatic lung and significantly elevated in sputum, compared to controls, whereas S100A8 or S100A9 levels were not. Monomeric oxS100A8 was the major component in asthmatic sputum; modifications were similar to those generated by hypochlorous acid (HOCl) in vitro. Oxidized Met63/81/94 were variously present in S100A9 from asthmatic sputum, only oxidized Met63 was seen in control sputum.
    [Show full text]