DOCSLIB.ORG

Promotes Dendritic Cell Transmigration Derived Chemerin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Promotes Dendritic Cell Transmigration Derived Chemerin Endothelial Cell−Derived Chemerin Promotes Dendritic Cell Transmigration Safiye Gonzalvo-Feo, Annalisa Del Prete, Monika Pruenster, Valentina Salvi, Li Wang, Marina Sironi, Susanne This information is current as Bierschenk, Markus Sperandio, Annunciata Vecchi and of September 28, 2021. Silvano Sozzani J Immunol published online 27 January 2014 http://www.jimmunol.org/content/early/2014/01/25/jimmun ol.1302028 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2014/01/25/jimmunol.130202 Material 8.DCSupplemental 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 28, 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 © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published January 27, 2014, doi:10.4049/jimmunol.1302028 The Journal of Immunology Endothelial Cell–Derived Chemerin Promotes Dendritic Cell Transmigration Safiye Gonzalvo-Feo,*,1 Annalisa Del Prete,*,†,1 Monika Pruenster,‡ Valentina Salvi,† Li Wang,*,x Marina Sironi,* Susanne Bierschenk,‡ Markus Sperandio,‡ Annunciata Vecchi,* and Silvano Sozzani*,† ChemR23 is a chemotactic receptor expressed by APCs, such as dendritic cells, macrophages, and NK cells. Chemerin, the ChemR23 ligand, was detected by immunohistochemistry, to be associated with inflamed endothelial cells in autoimmune diseases, such as lupus erythematosus, psoriasis, and rheumatoid arthritis. This study reports that blood and lymphatic murine endothelial cells produce chemerin following retinoic acid stimulation. Conversely, proinflammatory cytokines, such as TNF-a, IFN-g, and LPS, or calcitriol, are not effective. Retinoic acid–stimulated endothelial cells promoted dendritic cell adhesion under shear stress conditions and transmigration in a ChemR23-dependent manner. Activated endothelial cells upregulated the expression of the Downloaded from atypical chemotactic receptor CCRL2/ACKR5, a nonsignaling receptor able to bind and present chemerin to ChemR23+ dendritic cells. Accordingly, activated endothelial cells expressed chemerin on the plasma membrane and promoted in a more efficient manner chemerin-dependent transmigration of dendritic cells. Finally, chemerin stimulation of myeloid dendritic cells induced the high-affinity binding of VCAM-1/CD106 Fc chimeric protein and promoted VCAM-1–dependent arrest to immobilized ligands under shear stress conditions. In conclusion, this study reports that retinoic acid–activated endothelial cells can promote myeloid and plasmacytoid dendritic cell transmigration across endothelial cell monolayers through the endogenous production of http://www.jimmunol.org/ chemerin, the upregulation of CCRL2, and the activation of dendritic cell b1 integrin affinity. The Journal of Immunology, 2014, 192: 000–000. he correct localization of dendritic cells (DC) to peripheral the last 6 or 7 aa from the C terminus (7). Various proteases mediate tissues and secondary lymphoid organs is a crucial event for chemerin processing; these include neutrophil serine proteases and T optimal immune responses (1). Multiple chemotactic signals proteases from the coagulation and fibrinolytic cascades (8). Many regulate the trafficking of myeloid DC (mDC) and plasmacytoid DC tissues express chemerin in a constitutive manner, although the (pDC), the two main circulating DC subsets (2). Chemotactic ago- nature of the producing cells is still largely unknown (6). ChemR23, by guest on September 28, 2021 nists active on DC include chemokines, cytokines, formyl peptides, the functional chemerin receptor (also known as CMKLR1 in complement fragments, and bioactive lipid molecules (3, 4). humans and Dez in the mouse), is a G protein–coupled receptor ex- Chemerin was originally described as the product of the Tazarotene- pressed in various leukocyte populations, including mDC, pDC, induced gene 2 (Tig2) in stimulated skin cultures of psoriatic patients monocytes, macrophages, and NK cells (9–13). More recently, two (5) and subsequently purified from ascetic fluids from ovarian can- other high-affinity chemerin receptors were described, as follows: cer patients and synovial exudates from rheumatoid arthritis patients GPR1, a poor signaling receptor mainly expressed in the CNS, and (6). Chemerin is secreted as a poorly active precursor that is con- CCRL2/ACKR5, a member of the atypical chemokine receptor verted into a bioactive agonist following the proteolytic removal of family (also known as LCCR in the mouse) (8, 14). CCRL2 is a nonsignaling receptor that was proposed to bind and concentrate bioactive chemerin to ChemR23-positive cells (15, 16). *Humanitas Clinical and Research Center, Rozzano 20089, Italy; †Department of Chemerin is normally present in circulation of healthy subjects, Molecular and Translational Medicine, University of Brescia, Brescia 25123, Italy; and its levels are upregulated in many inflammatory conditions, ‡Walter Brendel Center for Experimental Medicine, Ludwig-Maximilians-Universi- x such as lupus erythematosus, psoriasis, rheumatoid arthritis, and ta¨t, Munchen€ 81377, Germany; and Department of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Crohn’s disease (17). We previously reported chemerin immuno- 1S.G.-F. and A.D.P. equally contributed to this work. staining in decidual cells during early pregnancy, with highest Received for publication July 31, 2013. Accepted for publication December 28, 2013. levels present in stromal and extravillous trophoblast cells (18). In addition, chemerin was found to be associated with tubular epi- This work was supported by the Italian Association for Cancer Research; Italian Ministry of Health (Progetto Giovani Ricercatori 2007); Ministero dell’Istruzione thelial cells and renal lymphatic endothelial cells in patients with Universita` e Ricerca; Fondazione Berlucchi; European Project Innovative Medicines lupus nephritis but not in normal kidneys (19). Chemerin expres- Initiative Joint Undertaking–funded project BeTheCure, Contract 115142-2; and Eurostars ChemExit 7306/8. sion also colocalized with high endothelial venules in lymph nodes and with inflamed endothelial cells in skin biopsies obtained from Address correspondence and reprint requests to Prof. Silvano Sozzani, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Bres- patients with autoimmune diseases, such as systemic lupus erythe- cia 25123, Italy. E-mail address: [email protected] matosus, lichen planus, and psoriasis (10, 11, 20). However, at The online version of this article contains supplemental material. present it is unknown whether endothelial cells produce chemerin or Abbreviations used in this article: DC, dendritic cell; KO, knockout; mDC, myeloid only bind and present on their surface the protein. Of note, in all DC; MELC, mouse lymphatic endothelial cell line; pDC, plasmacytoid DC; RA, cases, chemerin+ endothelial cells were surrounded by ChemR23+ retinoic acid. DC postulating a role for the ChemR23/chemerin axis in DC traf- Copyright Ó 2014 by The American Association of Immunologists, Inc. 0022-1767/14/$16.00 ficking across endothelial cell barriers. www.jimmunol.org/cgi/doi/10.4049/jimmunol.1302028 2 ENDOTHELIAL CELLS EXPRESS BIOLOGICAL ACTIVE CHEMERIN The aim of the current study was to investigate the regulation cDNA reverse-transcription kit from Applied Biosystems, following man- of chemerin expression and production by vascular and lymphatic ufacturer’s instructions. RT-PCR was performed on cDNA samples using endothelial cells and to evaluate the role of the chemerin/ChemR23 a Power SYBR Green PCR master mix (Applied Biosystems, Warrington, U.K.) and specific primers. RT-PCRs were performed on a 7900HT Fast axis in the transmigration of DC subsets across endothelial cell Real-Time PCR System machine according to manufacturer’s guidelines barriers. (Applied Biosystems). The primer pairs used were as follows: mouse ChemR23 (forward: 59-CCATGTGCAAGATCAGCAAC-39, reverse: 59- GCAGGAAGACGCTGGTGTA-39), CCRL2 (forward: 59-TGTGTTTCCTG- Materials and Methods CTTCCCCTG-39,reverse:59-CGAGGAGTGGAGTCCGACAA-39), mCCR1 Reagents (forward: 59-CTGCCCCCCCTGTATTCTCT-39,reverse:59-GACATTGCCCA- CCACTCCA-39), mCCR2 (forward: 59-CTACGATGATGGTGAGCCTTGTC- DMEM (4.5 g/L glucose), RPMI 1640 medium, heat-inactivated FBS, 39,reverse:59-AGCTCCAATTTGCTTCACACTG-39), mCCR7 (forward: 59- penicillin/streptomycin, nonessential amino acids, and Na pyruvate were TGGTGGTGGCTCTCCTTGTC-39,reverse:59-CCTCATCTTGGCAGAAGC- from Lonza (Verviers, Belgium). The 1a,25 dihydroxyvitamin D3 (calci- ACA-39), mCCL3 (forward: 59-CATATGGAGCTGACACCCCG-39,reverse:59- triol), all trans retinoic acid (RA), BSA (A2934), gelatin type B from TCTTCCGGCTGTAGGAGAAGC-39), mCCL4 (forward: 59-GCCCTCTCTC- bovine skin, and heparin were from Sigma-Aldrich (St. Louis, MO). Re- TCCTCTTGCT-39,reverse:59-GAGGGTCAGAGCCCATTG-39),
Load more

Recommended publications
  • In a Lung Disease Model an Anti-Inflammatory Activity Of
    Mouse ChemR23 Is Expressed in Dendritic Cell Subsets and Macrophages, and Mediates an Anti-Inflammatory Activity of Chemerin in a Lung Disease Model This information is current as of September 29, 2021. Souphalone Luangsay, Valérie Wittamer, Benjamin Bondue, Olivier De Henau, Laurie Rouger, Maryse Brait, Jean-Denis Franssen, Patricia de Nadai, François Huaux and Marc Parmentier J Immunol 2009; 183:6489-6499; Prepublished online 19 Downloaded from October 2009; doi: 10.4049/jimmunol.0901037 http://www.jimmunol.org/content/183/10/6489 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2009/10/20/jimmunol.090103 Material 7.DC1 References This article cites 60 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/183/10/6489.full#ref-list-1 by guest on September 29, 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
    [Show full text]
  • Neutrophil Chemoattractant Receptors in Health and Disease: Double-Edged Swords
    Cellular & Molecular Immunology www.nature.com/cmi REVIEW ARTICLE Neutrophil chemoattractant receptors in health and disease: double-edged swords Mieke Metzemaekers1, Mieke Gouwy1 and Paul Proost 1 Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview
    [Show full text]
  • Dampening Cytokine Production HIV Susceptibility Locus Targeting
    RESEARCH HIGHLIGHTS Dampening cytokine production circulating pDCs uniquely express a chemokine receptor known as che- mokine-like receptor 1 (CMKLR1, also known as ChmeR23 or DEZ) that Although TRAIL receptor (TRAIL-R) signaling is associated with distinguishes them from mDCs. The ligand for CMKLR1, chemerin, was apoptosis induction in vitro, the in vivo function of TRAIL-R is not detectable in human sera. The mRNA of chemerin was also present in well understood. In Immunity, Winoto and colleagues show that the many tissues, including the liver, pancreas and adrenal glands. Chemerin innate immune response to certain pathogens is enhanced in TRAIL- attracted blood pDCs but not mDCs. Because active chemerin requires R-deficient mice. Increased clearance of mouse cytomegalovirus proteolytic processing, the presence of these enzymes at sites of inflam- from the spleen was associated with increased IL-12, IFN-α and mation and tissue damage may serve to recruit pDCs. PTL IFN-β production by dendritic cells and macrophages. Likewise, J. Immunol. 174, 244–251 (2005) Toll-like receptor 2 (TLR2), TLR3 and TLR4 stimulation, along with mycobacterial stimulation, enhanced cytokine production and also induced upregulation of TRAIL expression by these innate immune HIV susceptibility locus cells. Specifically, TRAIL-R deficiency affected re-expression of IκBα at later times after TLR signaling. These data show TRAIL-R The CC chemokine CCL31L, also called MIP-1αP, has a signaling normally negatively regulates the cytokine response of the suppressive function in HIV infection. CCL31L is the main ligand innate immune system. JDKW for the HIV co-receptor CCR5. In Science, Gonzalez et al.
    [Show full text]
  • The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature
    International Journal of Molecular Sciences Review The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature Jan Korbecki 1 , Klaudyna Kojder 2, Patrycja Kapczuk 1, Patrycja Kupnicka 1 , Barbara Gawro ´nska-Szklarz 3 , Izabela Gutowska 4 , Dariusz Chlubek 1 and Irena Baranowska-Bosiacka 1,* 1 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] (J.K.); [email protected] (P.K.); [email protected] (P.K.); [email protected] (D.C.) 2 Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-281 Szczecin, Poland; [email protected] 3 Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] 4 Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wlkp. 72 Av., 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-914661515 Abstract: Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influ- ence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 Citation: Korbecki, J.; Kojder, K.; Kapczuk, P.; Kupnicka, P.; (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors— Gawro´nska-Szklarz,B.; Gutowska, I.; CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8.
    [Show full text]
  • The Atypical Receptor Ccrl2 (C-C Chemokine Receptor-Like 2) Does Not Act As a Decoy Receptor in Endothelial Cells
    ORIGINAL RESEARCH published: 06 October 2017 doi: 10.3389/fimmu.2017.01233 The Atypical Receptor CCRL2 (C-C Chemokine Receptor-Like 2) Does Not Act As a Decoy Receptor in Endothelial Cells Chiara Mazzotti1, Vincenzo Gagliostro1, Daniela Bosisio1, Annalisa Del Prete1,2, Laura Tiberio1, Marcus Thelen 3 and Silvano Sozzani1,2* 1 Laboratory of Experimental Immunology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy, 2 Humanitas Clinical and Research Centre, Rozzano, Italy, 3 Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland C-C chemokine receptor-like 2 (CCRL2) is a non-signaling seven-transmembrane domain (7-TMD) receptor related to the atypical chemokine receptor (ACKR) family. ACKRs bind chemokines but do not activate G protein-dependent signaling or cell functions. ACKRs were shown to regulate immune functions in vivo by their ability Edited by: to scavenge chemokines from the local environment. This study was performed to Ji Ming Wang, National Cancer Institute investigate whether CCRL2 shares two of the main characteristics of ACKRs, namely at Frederick, United States the ability to internalize and scavenge the ligands. Cell membrane analysis of CCRL2- Reviewed by: transfected cells revealed a weak, constitutive, ligand-independent internalization, and Santos Mañes, recycling of CCRL2, with a kinetics that was slower than those observed with ACKR3, Consejo Superior de Investigaciones Científicas a prototypic ACKR, or other chemotactic signaling receptors [i.e., chemokine-like (CSIC), Spain receptor 1 and C-X-C motif chemokine receptor 2]. Intracellularly, CCRL2 colocalized Diana Boraschi, Consiglio Nazionale with early endosome antigen 1-positive and Rab5-positive vesicles and with recycling Delle Ricerche (CNR), Italy compartments mainly characterized by Rab11-positive vesicles.
    [Show full text]
  • Part One Fundamentals of Chemokines and Chemokine Receptors
    Part One Fundamentals of Chemokines and Chemokine Receptors Chemokine Receptors as Drug Targets. Edited by Martine J. Smit, Sergio A. Lira, and Rob Leurs Copyright Ó 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32118-6 j3 1 Structural Aspects of Chemokines and their Interactions with Receptors and Glycosaminoglycans Amanda E. I. Proudfoot, India Severin, Damon Hamel, and Tracy M. Handel 1.1 Introduction Chemokines are a large subfamily of cytokines (50 in humans) that can be distinguished from other cytokines due to several features. They share a common biological activity, which is the control of the directional migration of leukocytes, hence their name, chemoattractant cytokines. They are all small proteins (approx. 8 kDa) that are highly basic, with two exceptions (MIP-1a, MIP-1b). Also, they have a highly conserved monomeric fold, constrained by 1–3 disulfides which are formed from a conserved pattern of cysteine residues (the majority of chemokines have four cysteines). The pattern of cysteine residues is used as the basis of their division into subclasses and for their nomenclature. The first class, referred to as CXC or a-chemokines, have a single residue between the first N-terminal Cys residues, whereas in the CC class, or b-chemokines, these two Cys residues are adjacent. While most chemokines have two disulfides, the CC subclass also has three members that contain three. Subsequent to the CC and CXC families, two fi additional subclasses were identi ed, the CX3C subclass [1, 2], which has three amino acids separating the N-terminal Cys pair, and the C subclass, which has a single disulfide.
    [Show full text]
  • Chemerin Is Associated with Markers of Inflammation and Components Of
    European Journal of Endocrinology (2009) 161 339–344 ISSN 0804-4643 CLINICAL STUDY Chemerin is associated with markers of inflammation and components of the metabolic syndrome but does not predict coronary atherosclerosis Michael Lehrke1, Alexander Becker2, Martin Greif2, Renee Stark3,Ru¨diger P Laubender4, Franz von Ziegler2, Corinna Lebherz2, Janine Tittus2, Maximilian Reiser5, Christoph Becker5, Burkhard Go¨ke1, Alexander W Leber2, Klaus G Parhofer1 and Uli C Broedl1 Departments of 1Internal Medicine II and 2Internal Medicine I, University of Munich, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany, 3Helmholtz-Zentrum, Munich, Germany, 4Institute for Medical Informatics, Biometry and Epidemiology (IBE) and 5Department of Radiology, University of Munich, Munich, Germany (Correspondence should be addressed to U C Broedl; Email: [email protected]) Abstract Objectives: Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology. Design: Serum chemerin levels were determined in 303 patients with stable typical or atypical chest pain who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed, or non-calcified. Results: Chemerin levels were highly correlated with high sensitivity C-reactive protein (rZ0.44, P!0.0001), interleukin-6 (rZ0.18, PZ0.002), tumor necrosis factor-a (rZ0.24, P!0.0001), resistin (rZ0.28, P!0.0001), and leptin (rZ0.36, P!0.0001) concentrations.
    [Show full text]
  • Chemerin-Activated Functions of CMKLR1 Are Regulated by G Protein- Coupled Receptor Kinase 6 (GRK6) and Β-Arrestin 2 in Inflammatory T Macrophages
    Molecular Immunology 106 (2019) 12–21 Contents lists available at ScienceDirect Molecular Immunology journal homepage: www.elsevier.com/locate/molimm Chemerin-activated functions of CMKLR1 are regulated by G protein- coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory T macrophages D. Stephen Serafina, Brittney Allyna,g, Maria F. Sassanob, Roman G. Timoshchenkoa, Daniel Mattoxa, Jaime M. Brozowskic,g, David P. Siderovskid, Young K. Truonge, ⁎ Denise Essermanf, Teresa K. Tarranta,g, Matthew J. Billarda,h, a Thurston Arthritis Research Center and the Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States b Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, United States c Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, United States d Department of Physiology & Pharmacology, West Virginia University, Morgantown, WV, 26506, United States e Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, United States f Yale School of Public Health, New Haven, CT 06510, United States g Duke University, Department of Medicine, Division of Rheumatology and Immunology, Durham, NC 27710, United States h Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, United States ARTICLE INFO ABSTRACT Keywords: Chemerin receptor (CMKLR1) is a G protein-coupled receptor (GPCR) implicated in macrophage-mediated in- Chemerin flammation and in several forms of human arthritis. Analogous to other GPCR, CMKLR1 is likely regulated by G G protein-coupled receptor kinase (GRK) protein-coupled receptor kinase (GRK) phosphorylation of intracellular domains in an activation-dependent Arrestin manner, which leads to recruitment and termination of intracellular signaling via desensitization and inter- Arthritis nalization of the receptor.
    [Show full text]
  • Chemerin Is a Novel Adipocyte-Derived Factor Inducing Insulin Resistance in Primary Human Skeletal Muscle Cells
    Diabetes Publish Ahead of Print, published online August 31, 2009 Chemerin and muscle insulin resistance CHEMERIN IS A NOVEL ADIPOCYTE-DERIVED FACTOR INDUCING INSULIN RESISTANCE IN PRIMARY HUMAN SKELETAL MUSCLE CELLS Henrike Sell†, Jurga Laurencikiene¶, Annika Taube†, Kristin Eckardt†, Andrea Cramer†, Angelika Horrighs†, Peter Arner¶ and Jürgen Eckel†. †Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany ¶Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. Running title: Chemerin and muscle insulin resistance Address correspondence to: Dr. Henrike Sell, E-mail: [email protected] Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org Submitted 24 February 2009 and accepted 10 August 2009. This is an uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association, publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals.org. Copyright American Diabetes Association, Inc., 2009 Chemerin and muscle insulin resistance Objective: Chemerin is an adipokine that affects adipogenesis and glucose homeostasis in adipocytes and increases with BMI in humans. This study aimed at investigating the regulation of chemerin release and its effects on glucose metabolism in skeletal muscle cells. Research Design and Methods: Human skeletal muscle cells were treated with chemerin to study insulin signaling, glucose uptake and activation of stress kinases. The release of chemerin was analyzed from in vitro differentiated human adipocytes and adipose tissue explants from 27 lean and 26 obese patients.
    [Show full text]
  • Expressıon and Functıonal Analysıs of Ccrl2 Atypıcal Chemokıne Receptor
    REPUBLIC OF TURKEY HACETTEPE UNIVERSITY INSTITUTE OF HEALTH SCIENCES EXPRESSION AND FUNCTIONAL ANALYSIS OF CCRL2 ATYPICAL CHEMOKINE RECEPTOR VARIANTS ON BREAST CANCER CELLS Dr. Parisa SARMADİ Tumor Biology and Immunology PhD THESIS ANKARA 2014 REPUBLIC OF TURKEY HACETTEPE UNIVERSITY INSTITUTE OF HEALTH SCIENCES EXPRESSION AND FUNCTIONAL ANALYSIS OF CCRL2 ATYPICAL CHEMOKINE RECEPTOR VARIANTS ON BREAST CANCER CELLS Dr. Parisa SARMADİ Tumor Biology and Immunology PhD THESIS Advisor of Thesis Assoc. Prof. Dr. Güneş ESENDAĞLI ANKARA 2014 iii iv ACKNOWLEDGEMENTS I would like to express my deepest gratitude and appreciation to my advisor Assoc. Prof. Dr. Güneş ESENDAĞLI for his support, encouragement, and guidance during all parts of my PhD study. I would like to express my deepest gratitude to Prof. Dr. Emin KANSU for his constitutive support and gentle and kind attitude; also, for his passion in science and transferring it to and inspiring students. I deeply and faithfully thank Prof. Dr. Dicle GÜÇ for her continuous support, kind-heartedness and guidance and for sharing her knowledge and experiences. I would like to gratefully thank Prof. Dr. A. Lale DOĞAN for her support, delicacy and kindness. I would like to cordially express my deepest and infinite gratitude and thankfulness to Asst. Prof. Dr. Hande CANPINAR for her support. I would like to gratefully thank Assoc. Prof. Dr. Güldal YILMAZ from Pathology Department at Gazi University for the great Immunohistochemistry analysis of breast cancer tissues. I would like to thank Asst. Prof. Dr. Füsun ÖZMEN for her kind attitude and support. I would like to gratefully thank Prof. Dr. Petek KORKUSUZ from Histology and Embryology Department and Prof.
    [Show full text]
  • Levels of Chemerin and Interleukin 8 in the Synovial Fluid of Patients with Inflammatory Arthritides and Osteoarthritis E
    Levels of chemerin and interleukin 8 in the synovial fluid of patients with inflammatory arthritides and osteoarthritis E. Valcamonica1,2, C.B. Chighizola3,4, D. Comi1, O. De Lucia1, L. Pisoni1, A. Murgo1, V. Salvi5, S. Sozzani5,6, P.L. Meroni1,3,4 1Division of Rheumatology, Istituto G. Pini, Milan, Italy; 2Doctorate Course in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy; 3Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; 4Immunorheumatological Research Laboratory, Istituto Auxologico Italiano, Milan, Italy: 5Department of Molecular and Translation Medicine, University of Brescia, Brescia, Italy; 6Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Abstract Objective Chemerin and interleukin (IL)-8 are pro-inflammatory mediators whose role in joint inflammation and cartilage degradation has been demonstrated in in-vitro findings. Studies on their presence in synovial fluid (SF) samples may offer further information on their pathogenic role. The aim of this study was to investigate SF chemerin and IL-8 levels in patients with different joint diseases. Methods 37 patients were enrolled: 18 with rheumatoid arthritis (RA), 8 with psoriatic arthritis (PsA) and 11 with osteoarthritis (OA). 41 SF samples were obtained by arthrocentesis in case of knee synovitis. Serum samples were obtained from 13 patients (4 with RA, 6 with PsA and 3 with OA) at the time of arthrocentesis. Chemerin, IL-8, TNF-α and IL-6 levels were measured using commercially available ELISA kits. Immunohistochemical analysis of synovial RA specimens was also performed. Results No difference in chemerin SF levels emerged between patients with immune-mediated inflammatory arthritides and those with OA (p=0.0656), while subjects with inflammatory arthritis displayed significantly higher levels of SF IL-8 compared to OA (p=0.0020).
    [Show full text]
  • Functional Expression of CCL8 and Its Interaction with Chemokine Receptor CCR3 Baosheng Ge*, Jiqiang Li, Zhijin Wei, Tingting Sun, Yanzhuo Song and Naseer Ullah Khan
    Ge et al. BMC Immunology (2017) 18:54 DOI 10.1186/s12865-017-0237-5 RESEARCH ARTICLE Open Access Functional expression of CCL8 and its interaction with chemokine receptor CCR3 Baosheng Ge*, Jiqiang Li, Zhijin Wei, Tingting Sun, Yanzhuo Song and Naseer Ullah Khan Abstract Background: Chemokines and their cognate receptors play important role in the control of leukocyte chemotaxis, HIV entry and other inflammatory diseases. Developing an effcient method to investigate the functional expression of chemokines and its interactions with specific receptors will be helpful to asses the structural and functional characteristics as well as the design of new approach to therapeutic intervention. Results: By making systematic optimization study of expression conditions, soluble and functional production of chemokine C-C motif ligand 8 (CCL8) in Escherichia coli (E. coli) has been achieved with approx. 1.5 mg protein/l culture. Quartz crystal microbalance (QCM) analysis exhibited that the purified CCL8 could bind with −7 C-C chemokine receptor type 3 (CCR3) with dissociation equilibrium constant (KD)as1.2×10 Minvitro. Obvious internalization of CCR3 in vivo could be detected in 1 h when exposed to 100 nM of CCL8. Compared with chemokine C-C motif ligand 11 (CCL11) and chemokine C-C motif ligand 24 (CCL24), a weaker chemotactic effect of CCR3 expressing cells was observed when induced by CCL8 with same concentration. Conclusion: This study delivers a simple and applicable way to produce functional chemokines in E. coli. The results clearly confirms that CCL8 can interact with chemokine receptor CCR3, therefore, it is promising area to develop drugs for the treatment of related diseases.
    [Show full text]