{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:52:54Z","timestamp":1760921574619,"version":"3.37.3"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T00:00:00Z","timestamp":1534204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.0764.14","G.0D25.17N"],"award-info":[{"award-number":["G.0764.14","G.0D25.17N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012220","name":"Hercules Foundation","doi-asserted-by":"publisher","award":["AKUL\/11\/31"],"award-info":[{"award-number":["AKUL\/11\/31"]}],"id":[{"id":"10.13039\/100012220","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002749","name":"Federaal Wetenschapsbeleid","doi-asserted-by":"publisher","award":["P7\/40"],"award-info":[{"award-number":["P7\/40"]}],"id":[{"id":"10.13039\/501100002749","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C16\/17\/010","GOA\/13\/014"],"award-info":[{"award-number":["C16\/17\/010","GOA\/13\/014"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To recruit leucocytes to an inflammatory site, chemokine binding to glycosaminoglycans (<jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content>s) is critical. Therefore, strategies to interfere with this interaction, aiming at the production of anti\u2010inflammatory agents, were developed. These include production of modified chemokines without affinity for G protein\u2010coupled receptors but with enhanced affinity for <jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content>s. Such modified chemokines compete with functional chemokines for <jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content> binding, prevent chemokine immobilization and presentation, and inhibit leucocyte migration. In addition to modified chemokines, a <jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content>\u2010binding peptide consisting of the 30 <jats:styled-content style=\"fixed-case\">COOH<\/jats:styled-content>\u2010terminal residues of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9, that is <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103), inhibited <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>8\u2010 and monosodium urate crystal\u2010induced neutrophil migration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We wanted to explore whether interference with chemokine\u2010<jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content> interactions by <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103) reduces inflammation in neutrophil\u2010dependent dinitrofluorobenzene\u2010induced contact hypersensitivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For this study, we evaluated several inflammatory parameters, including ear swelling and the levels of chemokines, cytokines, proteases and neutrophils in the ears of dinitrofluorobenzene\u2010induced mice treated with <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103) or buffer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One intravenous injection of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103), just before painting with dinitrofluorobenzene on the ear, did not affect protein levels of the major murine neutrophil attractant, that is <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>6, in this contact hypersensitivity model. However, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2 and matrix metalloproteinase\u20109 (MMP\u20109) protein concentrations and peroxidase activity in challenged ears were reduced. In addition, intravenous injection of the <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9\u2010derived peptide led to a reduced ear swelling response, indicating that the locally produced chemokines were hindered to attract leucocytes. The inhibiting potential of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103) was explained by its competition for <jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content> binding with <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>1, <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>6 and <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>3 and inhibition of transendothelial migration of neutrophils to <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>6.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103) peptide inhibited dinitrofluorobenzene\u2010induced infiltration of neutrophils and neutrophil\u2010dependent inflammation in ears. Therefore, <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>9(74\u2010103) may be a lead molecule for the development of therapeutic peptides or peptide derivatives that compete with functional chemokines for <jats:styled-content style=\"fixed-case\">GAG<\/jats:styled-content> binding.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13227","type":"journal-article","created":{"date-parts":[[2018,7,6]],"date-time":"2018-07-06T08:39:29Z","timestamp":1530866369000},"page":"1333-1344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti\u2010inflammatory effects of the <scp>GAG<\/scp>\u2010binding <scp>CXCL<\/scp>9(74\u2010103) peptide in dinitrofluorobenzene\u2010induced contact hypersensitivity in mice"],"prefix":"10.1111","volume":"48","author":[{"given":"Vincent","family":"Vanheule","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Crijns","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fariba","family":"Poosti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Ruytinx","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nele","family":"Berghmans","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Gerlza","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Institute of Pharmaceutical Sciences University of Graz Graz Austria"},{"name":"Antagonis Biotherapeutics GmbH Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Ronsse","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00ebmie","family":"P\u00f6rtner","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Matthys","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas J.","family":"Kungl","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Institute of Pharmaceutical Sciences University of Graz Graz Austria"},{"name":"Antagonis Biotherapeutics GmbH Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghislain","family":"Opdenakker","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie","family":"Struyf","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0133-5545","authenticated-orcid":false,"given":"Paul","family":"Proost","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology Department of Microbiology and Immunology Rega Institute for Medical Research KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2008.00741.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12061"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/b100916h"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809637200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05817"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004952"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-014-9551-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.11.012"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085699"},{"issue":"891","key":"e_1_2_7_11_1","first-page":"11","article-title":"Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells","volume":"22","author":"Rot A","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2017.06.009"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016303"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.007724"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-266072"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80422-5"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.018"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.12.3853"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405392200"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071513"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2014.08.004"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.11.018"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228456"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0334864100"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.082552"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.6991"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5776"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.07.029"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.5.3447"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0108061"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.12.008"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.05.037"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1233"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2011.02832.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.284"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(03)00017-8"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130062"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.16"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.649855"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1541"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2371"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20130069"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.6885"},{"key":"e_1_2_7_44_1","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.4049\/jimmunol.163.11.6155","article-title":"NH2\u2010 and COOH\u2010terminal truncations of murine granulocyte chemotactic protein\u20102 augment the in\u00a0vitro and in\u00a0vivo neutrophil chemotactic potency","volume":"163","author":"Wuyts A","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.043299"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02089.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.10.013"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2000.17721.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543780903535867"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-493924"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-542480"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.04.006"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199802)20:2<156::AID-BIES8>3.0.CO;2-R"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.11.001"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00530"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs308"},{"key":"e_1_2_7_57_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1182\/blood.V70.5.1630.1630","article-title":"Peroxidase\u2010containing microgranules in human neutrophils: physical, morphological, cytochemical, and secretory properties","volume":"70","author":"Parmley RT","year":"1987","journal-title":"Blood"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.1997.02719.x"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.69.6.851"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.8.2673"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03760.x"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)02023-3"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1989.tb23997.x"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.13227","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T18:19:45Z","timestamp":1694801985000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.13227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,14]]},"references-count":62,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/cea.13227"],"URL":"https:\/\/doi.org\/10.1111\/cea.13227","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"type":"print","value":"0954-7894"},{"type":"electronic","value":"1365-2222"}],"subject":[],"published":{"date-parts":[[2018,8,14]]},"assertion":[{"value":"2017-08-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}