DOCSLIB.ORG

Calgranulins S100A8 and S100A9 Are Negatively Regulated by Glucocorticoids in a C-Fos-Dependent Manner and Overexpressed Throughout Skin Carcinogenesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Calgranulins S100A8 and S100A9 Are Negatively Regulated by Glucocorticoids in a C-Fos-Dependent Manner and Overexpressed Throughout Skin Carcinogenesis Oncogene (2002) 21, 4266 ± 4276 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Calgranulins S100A8 and S100A9 are negatively regulated by glucocorticoids in a c-Fos-dependent manner and overexpressed throughout skin carcinogenesis Christoer Gebhardt1, Ute Breitenbach2, Jan Peter Tuckermann3, Bernd Thilo Dittrich1, Karl Hartmut Richter1 and Peter Angel*,1 1Deutsches Krebsforschungszentrum, Division of Signal Transduction and Growth Control, 69120 Heidelberg, Germany The two calgranulins S100A8 and S100A9 were found to the S100 protein family of highly homologous low be dierentially expressed at sites of acute and chronic molecular weight calcium binding proteins (reviewed in¯ammation. Here we have employed the phorbol ester- by Donato, 2001). The calgranulins S100A8 and induced multistage skin carcinogenesis protocol in mice S100A9 can form a noncovalent heterodimer protein to determine the expression of both genes in in¯amed complex called calprotectin, which antagonizes the skin and in skin tumors. We show that expression is monomer functions (Newton and Hogg, 1998). coordinately induced by the phorbol ester TPA in Calgranulins are characterized by cell type-speci®c epithelial cells as well as in®ltrating leukocytes. By expression in cells of epithelial, myeloid and endothe- comparing S100A8 and S100A9 mRNA levels in wild lial origin and accumulation at sites of acute and type and c-Fos de®cient mice (c-fos7/7) we found that chronic in¯ammation (e.g. rheumatoid arthritis, cystic expression is negatively regulated by c-Fos/AP-1. ®brosis, psoriasis, allergic dermatitis, in¯ammatory Glucocorticoids, which exhibit potent anti-in¯ammatory bowel diseases) (reviewed by Donato, 2001). Recently and anti-tumor promoting activities repressed TPA- a functional interaction of the calgranulin family mediated S100A8 and S100A9 induction in wild type, member S100A12 with the receptor for advanced but not in c-fos7/7 mice, thus identifying both genes as glycation end products (RAGE) was discovered the ®rst examples of AP-1 target genes whose repression (Hofmann et al., 1999). RAGE was found to be of TPA-induced transcription by glucocorticoids depends involved in in¯ammation (Hofmann et al., 1999), in on c-Fos. Finally, we show that enhanced expression is tumor growth and metastasis (Taguchi et al., 2000), in not restricted to the initial TPA-induced in¯ammatory wound healing (Goova et al., 2001), and the pathology response but is observed at all stages of skin carcinogen- of certain diseases such as diabetes and Alzheimer's esis. These data identify S100A8 and S100A9 as novel, disease (reviewed by Schmidt et al., 2000). tumor-associated genes and may point to an as yet The calgranulins S100A8 and S100A9 are currently unrecognized function of both genes in the development attracting much interest because of their wide range of of epithelial skin tumors. possible intracellular as well as extracellular functions Oncogene (2002) 21, 4266 ± 4276. doi:10.1038/sj.onc. (reviewed by Donato, 2001). For example, both 1205521 proteins have been suggested to aect alteration of the cytoskeleton and cell shape, signal transduction, Keywords: AP-1; epidermis; in¯ammation; papilloma; exclusive carrying of arachidonic acids (Kerkho et tumor promoter al., 1999), and modulation of intracellular calcium (Schafer and Heizmann, 1996). Moreover, S100A8 and S100A9 have been described to be involved in Introduction in¯ammatory conditions (Odink et al., 1987; Brandt- zaeg et al., 1987). Approximately 45% of the S100A8 (MRP-8; CP-10; calgranulin A; cystic ®brosis cytoplasmic protein fraction of neutrophils is com- antigen), S100A9 (MRP-14; calgranulin B) and prised of S100A8 and S100A9 underlining their S100A12 (calgranulin C; EN-RAGE) are members of importance in in¯ammation (Edgeworth et al., 1991). The release of these small proteins via a TPA (12-O- tetradecanoyl-13-phorbolacetate)-stimulated tubulin- dependent pathway (Rammes et al., 1997) into the *Correspondence: P Angel, Deutsches Krebsforschungszentrum, Division of Signal Transduction and Growth Control, Im extracellular space supports the importance of their Neuenheimer Feld 280, 69120 Heidelberg, Germany; extracellular functions which includes potent chemo- E-mail: [email protected] tactic activity, triggering of local in¯ammation, Current addresses: 2Beiersdorf AG, Hamburg, Germany; 3Division of regulation of adhesivity, transendothelial migration Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, of leukocytes and striking antimicrobial properties 69120 Heidelberg, Germany Received 10 October 2001; revised 6 March 2002; accepted 26 (Kerkho et al., 1998; Passey et al., 1999a; Steinbakk March 2002 et al., 1990). Expression of calgranulins S100A8/S100A9 C Gebhardt et al 4267 S100A8-de®cient mouse embryos exhibiting an embryonic lethal phenotype have revealed non-redun- dant functions of S100A8 protein during fetal im- plantation (Passey et al., 1999b), and coordinate expression and secretion of S100A8 and S100A9 proteins have been observed during wound healing and in hyperthickened epithelium (Thorey et al., 2001). However, neither regulatory mechanisms of gene expression, nor the speci®c functions of the calgranu- lins S100A8 and S100A9 in in¯ammation-associated processes have yet been identi®ed conclusively. A frequently used model of acute in¯ammation is TPA- induced edema formation in the skin as the initial part of the chemically induced multistage skin carcinogenesis protocol (reviewed by Marks and FuÈ rstenberger, 1990; Bowden et al., 1994; Yuspa et al., 1996). Application of TPA to the skin causes swelling associated with increased vascular permeabil- ity and rapid in¯ux of neutrophil granulocytes and mononuclear cells into the skin. Cotreatment with glucocorticoids, which are in widespread medical use to inhibit in¯ammatory processes, interferes with both edema formation and the development of papilloma and carcinoma (Belman and Troll, 1972). Recently, we have applied PCR-based suppression subtraction hybridization to establish a cDNA library of TPA-inducible genes in mouse skin (Breitenbach et al., 2001). Two of these clones turned out to encode the calgranulins S100A8 and S100A9. Here we have determined cell type-speci®c expression of both genes in the initial TPA-induced in¯ammatory response and during various stages of skin carcinogenesis. Wild type and c-Fos de®cient mice (c-fos7/7) were used to establish the critical role of c-Fos in calgranulins S100A8 and S100A9 expression and repression by anti-in¯ammatory glucocorticoids. Results TPA coordinately induces calgranulins S100A8 and S100A9 expression in skin Figure 1 PKC-speci®c induction of calgranulins S100A8 and In an eort to identify genes in murine skin, which are S100A9 by TPA. (a) Induction of calgranulins S100A8 and transiently induced by tumor promoters, we isolated S100A9 by TPA in murine skin. TPA (10 nmol) in 100 ml acetone the two calgranulins S100A8 and S100A9 (Breitenbach was applied onto the backskin of C57BL/6 mice. After 0, 1, 4, 6 h et al., 2001). Induction kinetics revealed elevated mice were sacri®ced and RNA from skin was prepared. The level of calgranulins S100A8 and S100A9 transcripts was visualized by mRNA levels of S100A8 as well as S100A9 at 4 h Northern analysis. Rehybridization with a cDNA fragment of 18S after TPA treatment, whereas in the skin of control RNA was performed serving as loading control. One representa- treated animals only very low basal level expression of tive experiment out of three independent experiments using tissue both genes could be detected. Maximal levels of pooled from three mice is shown. (b) PKC-speci®c inhibitors suppress TPA-mediated induction of S100A8 and S100A9. PMK- induction (over 100-fold) were reached at 6 h, which R3 keratinocytes (Rennecke et al., 1999) were treated with returned to almost basal levels after 12 h (Figure 1a acetone (7), 10 nmol TPA (TPA), 100 nmol PKC-inhibitors and data not shown). Similar to the induction of Goedecke 6983 or 100 nmol Goedecke 6976 dissolved in acetone. S100A8 and S100A9 in vivo in skin, in the previously Fifteen min before TPA addition. Expression of SPRR2A was described immortalized mouse keratinocyte cell line chosen for comparison. Cells were harvested for RNA prepara- tion 6 h thereafter and analysed as described in (a) PMK-R3 (Rennecke et al., 1999) expression can be eciently induced by TPA (Figure 1b). These data show that expression of both genes is coordinately induced by TPA and follow similar kinetics as genes, such as MMP3 and MMP13 (Tuckermann et compared to previously described TPA-responsive al., 1999). Oncogene Expression of calgranulins S100A8/S100A9 C Gebhardt et al 4268 AP-1, c-Fos (Wang et al., 1992). Surprisingly, in PKC-specific inhibitors suppress TPA-induced comparison to the faint expression of S100A8 and upregulation of S100A8 and S100A9 S100A9 in acetone-treated control skin of wild type Distinct isoforms of the protein kinase C (PKC) family mice the expression levels of the calgranulins S100A8 represent the major `receptor' of the phorbol ester TPA and S100A9 in skin of c-fos7/7 mice were constitu- to initiate signaling pathways to the nucleus. To tively and coordinately enhanced in the acetone-treated identify the PKC isozymes that might be involved in backskin (Figure 2) as well as in untreated backskin the upregulation of calgranulins S100A8 and S100A9 (data not shown). Similar to the ®ndings in wild type by TPA we measured induction
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]
  • Primary Antibodies Flyer
    Primary Antibodies Your choice of size and format Format Concentration Size CF® dye conjugates (13 colors) 0.1 mg/mL 100 or 500 uL Biotin, HRP or AP conjugates 0.1 mg/mL 100 or 500 uL R-PE, APC, or Per-CP conjugates 0.1 mg/mL 250 uL Purified, with BSA 0.1 mg/mL 100 or 500 uL Purified, BSA-free (Mix-n-Stain™ Ready) 1 mg/mL 50 uL Advantages Figure 1. IHC staining of human prostate Figure 2. Flow cytometry analysis of U937 • More than 1000 monoclonal antibodies carcinoma with anti-ODC1 clone cells with anti-CD31/PECAM clone C31.7, • Growing selection of monoclonal rabbit ODC1/485. CF647 conjugate (blue) or isotype control (orange). antibodies • Validated in IHC and other applications Your choice of 13 bright and photostable CF® dyes • Choose from 13 bright and stable CF® dyes CF® dye Ex/Em (nm) Features • Also available with R-PE, APC, PerCP, HRP, AP, CF®405S 404/431 • Better fit for the 450/50 flow cytometer channel than Alexa Fluor® 405 or biotin CF®405M 408/452 • More photostable than Pacific Blue®, with less green spill-over • Purified antibodies available BSA-free, 1 mg/mL, • Compatible with super-resolution imaging by SIM ready to use for Mix-n-Stain™ labeling or other CF®488A 490/515 • Less non-specific binding and spill-over than Alexa Fluor® 488 conjugation • Very photostable and pH-insensitive • Compatible with super-resolution imaging by TIRF • Offered in affordable 100 uL size CF®543 541/560 • Brighter than Alexa Fluor® 546 CF®555 555/565 • Brighter than Cy®3 • Validated in multicolor super-resolution imaging by STORM CF®568
    [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]
  • Calprotectin and Calgranulin C Serum Levels in Bacterial Sepsis
    Diagnostic Microbiology and Infectious Disease 93 (2019) 219–226 Contents lists available at ScienceDirect Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio ☆ Calprotectin and calgranulin C serum levels in bacterial sepsis Eva Bartáková a,MarekŠtefan a,Alžběta Stráníková a, Lenka Pospíšilová b, Simona Arientová a,Ondřej Beran a, Marie Blahutová b, Jan Máca a,c,MichalHoluba,⁎ a Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, U Vojenské nemocnice 1200, 169 02 Praha 6, Czech Republic b Department of Clinical Biochemistry, Military University Hospital Prague, U Vojenské nemocnice 1200, 169 02 Praha 6, Czech Republic c Department of Anesthesiology and Intensive Care Medicine, University Hospital of Ostrava, 17. listopadu 1790/5, 708 52 Ostrava-Poruba, Czech Republic article info abstract Article history: The aim of this study was to evaluate the serum levels of calprotectin and calgranulin C and routine biomarkers in Received 26 March 2018 patients with bacterial sepsis (BS). The initial serum concentrations of calprotectin and calgranulin C were signif- Received in revised form 2 October 2018 icantly higher in patients with BS (n = 66) than in those with viral infections (n = 24) and the healthy controls Accepted 10 October 2018 (n = 26); the level of calprotectin was found to be the best predictor of BS, followed by the neutrophil- Available online 17 October 2018 lymphocyte count ratio (NLCR) and the level of procalcitonin (PCT). The white blood cell (WBC) count and the NLCR rapidly returned to normal levels, whereas PCT levels normalized later and the increased levels of Keywords: Sepsis calprotectin, calgranulin C, and C-reactive protein persisted until the end of follow-up.
    [Show full text]
  • Proteomic Analysis of Two Non-Bronchoscopic Methods of Sampling the Lungs of Patients with the Acute Respiratory Distress Syndrome (ARDS)
    Clin Proteom (2007) 3:30–41 DOI 10.1007/s12014-007-9002-8 Proteomic Analysis of Two Non-Bronchoscopic Methods of Sampling the Lungs of Patients with the Acute Respiratory Distress Syndrome (ARDS) Dong W. Chang & Giuseppe Colucci & Tomas Vaisar & Trevor King & Shinichi Hayashi & Gustavo Matute-Bello & Roger Bumgarner & Jay Heinecke & Thomas R. Martin & Guido M. Domenighetti Published online: 5 January 2008 # Humana Press Inc. 2007 Abstract BAL samples, 13.2% were increased in s-Cath compared to Objective The collection of lung fluid using a suction catheter mini-BAL, and 18.4% were decreased in s-Cath compared (s-Cath) and non-bronchoscopic bronchoalveolar lavage to mini-BAL. For each of the seven subjects, overabun- (mini-BAL) are two minimally invasive methods of sampling dance analysis showed that the actual number of differen- the distal airspaces in patients with the acute respiratory tially expressed spots in the mini-BAL and s-Cath sample distress syndrome (ARDS). The objective of this study was to was more than the expected number if the samples were determine the similarity of the lung fluid samples recovered identical. There were nine proteins that were consistently by these methods using proteomic analysis. differentially expressed between the mini-BAL and s-Cath Methods Distal lung fluid samples were collected from samples. Of these nine proteins, five are abundantly found seven mechanically ventilated patients with ARDS using in neutrophils or airway epithelial cells, suggesting that the both s-Cath and mini-BAL in each patient and compared s-Cath may sample the bronchial airways to a greater extent using two-dimensional difference gel electrophoresis.
    [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]
  • The Roles of Calprotectin and Calgranulin C in <I>Campylobacter Jejuni</I>
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Masters Theses Graduate School 12-2017 The Roles of Calprotectin and Calgranulin C in Campylobacter jejuni Infection Janette Marie Shank University of Tennessee, [email protected] Follow this and additional works at: https://trace.tennessee.edu/utk_gradthes Recommended Citation Shank, Janette Marie, "The Roles of Calprotectin and Calgranulin C in Campylobacter jejuni Infection. " Master's Thesis, University of Tennessee, 2017. https://trace.tennessee.edu/utk_gradthes/5001 This Thesis is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Masters Theses by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a thesis written by Janette Marie Shank entitled "The Roles of Calprotectin and Calgranulin C in Campylobacter jejuni Infection." I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Master of Science, with a major in Microbiology. Jeremiah G. Johnson, Major Professor We have read this thesis and recommend its acceptance: Sarah L. Lebeis, Todd B. Reynolds Accepted for the Council: Dixie L. Thompson Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) The Roles of Calprotectin and Calgranulin C in Campylobacter jejuni Infection A Thesis Presented for the Master of Science Degree The University of Tennessee, Knoxville Janette Marie Shank December 2017 Copyright © 2017 by Janette M.
    [Show full text]
  • Serial Analysis of Gene Expression in Normal P53 Null Mammary Epithelium
    Oncogene (2002) 21, 6366 – 6376 ª 2002 Nature Publishing Group All rights reserved 0950 – 9232/02 $25.00 www.nature.com/onc Serial analysis of gene expression in normal p53 null mammary epithelium C Marcelo Aldaz*,1, Yuhui Hu1, Rachael Daniel1, Sally Gaddis1, Frances Kittrell2 and Daniel Medina2 1The University of Texas M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, Texas, TX 78957, USA; 2Baylor College of Medicine Department of Molecular and Cellular Biology, Houston, Texas, TX 77030, USA Much evidence has accumulated implicating the p53 gene function although activating mutations were also as of importance in breast carcinogenesis. However, observed. Usually p53 abnormalities associate with much still remains to be uncovered on the specific poorer clinical outcome. This, likely, is the consequence downstream pathways influenced by this important of the known critical roles of p53 in regulating the cell activator/repressor of transcription. This study investi- cycle, apoptosis, DNA repair and maintaining genome gated the effects of a p53 null genotype on the stability (Levine, 1997). The loss of wild type p53 transcriptome of ‘normal’ mouse mammary epithelium function is clearly an important event in breast using a unique in vivo model of preneoplastic transforma- tumorigenesis as documented both in human and murine tion. We used SAGE for the comparative analysis of p53 systems (Donehower et al., 1995; Elledge and Allred, wild type (wt) and null mammary epithelium unexposed 1994). However, the exact mechanisms by which such and exposed to hormonal stimulation. Analysis of the lack of normal gene function leads to cancer formation hormone exposed samples provided a comprehensive view and progression are only beginning to be understood.
    [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]
  • Gene Expression Signatures and Biomarkers of Noninvasive And
    Oncogene (2006) 25, 2328–2338 & 2006 Nature Publishing Group All rights reserved 0950-9232/06 $30.00 www.nature.com/onc ORIGINAL ARTICLE Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics GM Nagaraja1, M Othman2, BP Fox1, R Alsaber1, CM Pellegrino3, Y Zeng2, R Khanna2, P Tamburini3, A Swaroop2 and RP Kandpal1 1Department of Biological Sciences, Fordham University, Bronx, NY, USA; 2Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA and 3Bayer Corporation, West Haven, CT, USA We have characterized comprehensive transcript and Keywords: representational difference analysis; micro- proteomic profiles of cell lines corresponding to normal arrays; proteomics; breast carcinoma; biomarkers; breast (MCF10A), noninvasive breast cancer (MCF7) and copper homeostasis invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete con- Introduction cordance withmicroarray results, and also led to the identification of some differentially expressed genes such The transformation of a normal cell into a cancer cell as lysyl oxidase, copper transporter ATP7A, EphB6, has been correlated to altered expression of a variety of RUNX2 and a variant of RUNX2. The altered transcripts genes (Perou et al., 2000; Becker et al., 2005). The identified by microarray analysis were involved in cell–cell expression of some of these genes is a direct result of or cell–matrix interaction, Rho signaling, calcium home- sequence mutation, whereas other changes occur due to ostasis and copper-binding/sensitive activities.
    [Show full text]