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* Skip to Article Content * Skip to Article Information Search withinThis JournalAnywhere * Search term Advanced Search Citation Search * Search term Advanced Search Citation Search Login / Register Arthritis & Rheumatism Volume 60, Issue 9 p. 2805-2816 Systemic Sclerosis Free to Read NUCLEAR AUTOANTIGEN CENP-B TRANSACTIVATION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR VIA CHEMOKINE RECEPTOR 3 IN VASCULAR SMOOTH MUSCLE CELLS Geneviève Robitaille, Geneviève Robitaille Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Marie-Soleil Christin, Marie-Soleil Christin Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Isabelle Clément, Isabelle Clément Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Jean-Luc Senécal, Jean-Luc Senécal Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Yves Raymond, Corresponding Author Yves Raymond * yves.raymond@umontreal.ca Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Laboratory for Research in Autoimmunity, Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, CanadaSearch for more papers by this author Geneviève Robitaille, Geneviève Robitaille Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Marie-Soleil Christin, Marie-Soleil Christin Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Isabelle Clément, Isabelle Clément Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Jean-Luc Senécal, Jean-Luc Senécal Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Search for more papers by this author Yves Raymond, Corresponding Author Yves Raymond * yves.raymond@umontreal.ca Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, and Université de Montréal, Montréal, Québec, Canada Laboratory for Research in Autoimmunity, Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, CanadaSearch for more papers by this author First published: 27 August 2009 https://doi.org/10.1002/art.24765 Citations: 23 Read the full text About * * REFERENCES * RELATED * INFORMATION * PDF PDF Tools * Request permission * Export citation * Add to favorites * Track citation ShareShare Give access Share full text access Close modal Share full-text access Please review our Terms and Conditions of Use and check box below to share full-text version of article. I have read and accept the Wiley Online Library Terms and Conditions of Use -------------------------------------------------------------------------------- Shareable Link Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. Copy URL Share a link Share on * Email * Facebook * Twitter * LinkedIn * Reddit * Wechat ABSTRACT OBJECTIVE We have previously found that the CENP-B nuclear autoantigen, which is specifically targeted by autoantibodies in the limited cutaneous form of systemic sclerosis, behaved as a potent migratory factor for human pulmonary artery smooth muscle cells (PASMCs). Other recent studies have shown that several disease-associated autoantigens induced cell migration by interacting with various chemokine receptors. Prompted by this hypothesis, we undertook this study to determine whether CENP-B interacts with chemokine receptors on the surface of human PASMCs, to explore the relevant signaling pathways, and to characterize the effects of anti–CENP-B binding on SMC stimulation. METHODS To demonstrate the expression of specific chemokine receptors by human PASMCs at both the messenger RNA and protein levels, reverse transcription–polymerase chain reaction, immunoblotting, and flow cytometry analyses were performed. Desensitization studies and specific inhibitors were used to further identify the CENP-B target on the surface of human PASMCs. RESULTS Our data strongly suggested that CENP-B used chemokine receptor 3 (CCR3) to mediate human PASMCs signaling. Moreover, several lines of evidence indicated that CENP-B binding subsequently stimulated the cross-talk between CCR3 and epidermal growth factor receptor (EGFR) via a matrix metalloprotease–dependent mechanism that involved the processing of heparin-binding EGF-like growth factor. Transactivation of the EGFR through CCR3 was found to be a critical pathway that elicits MAP kinase activation and secretion of cytokines such as interleukin-8. Finally, anti–CENP-B autoantibodies were found to abolish this signaling pathway, thus preventing CENP-B from transactivating EGFR and exerting its cytokine-like activities toward vascular smooth muscle cells. CONCLUSION The identification of CENP-B as a CCR3 ligand opens up new perspectives for the study of the pathogenic role of anti–CENP-B autoantibodies. REFERENCES * 1 Allen SJ, Crown SE, Handel TM. Chemokine: receptor structure, interactions, and antagonism. 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Rheumatology. 4th ed. Philadelphia: Mosby Elsevier; 2008. p. 1361–7. * 40 Harris ML, Rosen A. Autoimmunity in scleroderma: the origin, pathogenetic role, and clinical significance of autoantibodies. Curr Opin Rheumatol 2003; 15: 778–84. * 41 Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2005; 35: 35–42. * 42 Boin F, Rosen A. Autoimmunity in systemic sclerosis: current concepts. Curr Rheumatol Rep 2007; 9: 165–72. CITING LITERATURE Volume60, Issue9 September 2009 Pages 2805-2816 * REFERENCES * RELATED * INFORMATION METRICS Citations: 23 DETAILS Copyright © 2009 by the American College of Rheumatology RESEARCH FUNDING * Studentship from Sclérodermie Québec * Studentships from the Canadian Institutes of Health Research * Fonds de la Recherche en Santé du Québec * Canadian Institutes of Health Research. Grant Numbers: MOP-68966, MOP-81252 * Sclérodermie Québec PUBLICATION HISTORY * Issue Online: 27 August 2009 * Version of Record online: 27 August 2009 * Manuscript accepted: 26 May 2009 * Manuscript received: 11 November 2008 Close Figure Viewer Return to Figure Previous FigureNext Figure Caption Download PDF back ADDITIONAL LINKS ABOUT WILEY ONLINE LIBRARY * Privacy Policy * Terms of Use * About Cookies * Manage Cookies * Accessibility * Wiley Research DE&I Statement and Publishing Policies * Developing World Access HELP & SUPPORT * Contact Us * Training and Support * DMCA & Reporting Piracy OPPORTUNITIES * Subscription Agents * Advertisers & Corporate Partners CONNECT WITH WILEY * The Wiley Network * Wiley Press Room Copyright © 1999-2023 John Wiley & Sons, Inc. All rights reserved The full text of this article hosted at iucr.org is unavailable due to technical difficulties. LOG IN TO WILEY ONLINE LIBRARY Email or Customer ID Password Forgot password? 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