{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:27:34Z","timestamp":1791098854330,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,9,12]],"date-time":"2013-09-12T00:00:00Z","timestamp":1378944000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"crossref","award":["B3413R"],"award-info":[{"award-number":["B3413R"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"crossref","award":["B3756F"],"award-info":[{"award-number":["B3756F"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Pre-Doctoral Associated Health Rehabilitation Research Fellowship"},{"name":"NIH","award":["1R03NS061033"],"award-info":[{"award-number":["1R03NS061033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Trafficking of autoreactive leukocytes across the blood\u2010nerve barrier and into peripheral nerves is an early pathological hallmark of Guillain\u2010Barr\u00e9 syndrome (<jats:styled-content style=\"fixed-case\">GBS<\/jats:styled-content>). Tumor necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1), a proinflammatory cytokine, promotes transendothelial migration by upregulating endothelial expression of inflammatory mediators, including <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content>, a chemokine implicated in <jats:styled-content style=\"fixed-case\">GBS<\/jats:styled-content>. We sought to determine the mechanism by which <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 induces expression and secretion of <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content> from peripheral nerve microvascular endoneurial endothelial cells (<jats:styled-content style=\"fixed-case\">PNMECs<\/jats:styled-content>). Expression of <jats:styled-content style=\"fixed-case\">CCL2 mRNA<\/jats:styled-content> and protein in quiescent <jats:styled-content style=\"fixed-case\">PNMEC<\/jats:styled-content> cultures was minimal. In contrast, cultures treated with <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 exhibited increased <jats:styled-content style=\"fixed-case\">CCL2 mRNA<\/jats:styled-content> and protein content, as well as protein secretion. Simvastatin significantly attenuated <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1\u2010induced <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content> secretion without affecting <jats:styled-content style=\"fixed-case\">CCL2 mRNA<\/jats:styled-content> or protein expression. Co\u2010incubation with geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, prevented the effect of simvastatin. By comparison, inhibiting protein isoprenylation with <jats:styled-content style=\"fixed-case\">GGTI<\/jats:styled-content>\u2010298, but not <jats:styled-content style=\"fixed-case\">FTI<\/jats:styled-content>\u2010277, mimicked the effect of simvastatin and significantly attenuated transendothelial migration <jats:italic>in vitro<\/jats:italic>. Inhibition of the monomeric <jats:styled-content style=\"fixed-case\">GTPase<\/jats:styled-content> Cdc42, but not Rac1 or <jats:styled-content style=\"fixed-case\">RhoA<\/jats:styled-content>\u2010C, attenuated <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1\u2010mediated <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content> secretion. <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1\u2010mediated trafficking of autoreactive leukocytes into peripheral nerves during <jats:styled-content style=\"fixed-case\">GBS<\/jats:styled-content> may proceed by a mechanism that involves Cdc42\u2010facilitated secretion of <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jns5.12032","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T19:46:19Z","timestamp":1375127179000},"page":"199-208","source":"Crossref","is-referenced-by-count":26,"title":["Cdc42 <scp>GTPases<\/scp> facilitate <scp>TNF<\/scp>\u2010\u03b1\u2010mediated secretion of <scp>CCL2<\/scp> from peripheral nerve microvascular endoneurial endothelial cells"],"prefix":"10.1111","volume":"18","author":[{"given":"Kelly A.","family":"Langert","sequence":"first","affiliation":[{"name":"Research Service, Department of Veterans Affairs Edward Hines, Jr. VA Hospital Hines IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia L.","family":"Von Zee","sequence":"additional","affiliation":[{"name":"Research Service, Department of Veterans Affairs Edward Hines, Jr. VA Hospital Hines IL USA"},{"name":"Department of Ophthalmology, Stritch School of Medicine Loyola University Chicago Maywood IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Evan B.","family":"Stubbs,","sequence":"additional","affiliation":[{"name":"Research Service, Department of Veterans Affairs Edward Hines, Jr. VA Hospital Hines IL USA"},{"name":"Department of Ophthalmology, Stritch School of Medicine Loyola University Chicago Maywood IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/116.5.1043"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1994.1051"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.649"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-9961(02)00007-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200302000-00022"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2002"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-1"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1160\/TH04-05-0297","article-title":"Fluvastatin increases the expression of adhesion molecules, monocyte chemoattractant protein\u20101 and tissue factor in HUVEC stimulated by patient IgG fractions containing antiphospholipid antibodies","volume":"93","author":"Dunoyer\u2010Geindre S","year":"2005","journal-title":"Thromb Haemost"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.57.9.1118"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070404"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00048-X"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5165"},{"key":"e_1_2_6_14_1","first-page":"328","article-title":"Experimental allergic neuritis (EAN) as a model for the immune\u2010mediated demyelinating neuropathies","volume":"152","author":"Hahn AF","year":"1996","journal-title":"Rev Neurol"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(03)00251-0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880180202"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01162-0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05440.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67665-9"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.59.3.746-750.1986"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.6.4.1204"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(00)00323-4"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276170"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/AN20120048"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R500017-JLR200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.195735"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5836-5"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.12.045"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21114"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00393-4"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2891"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5358"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5705"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024532715775"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00328-7"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0404.2003.00179.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07393.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/00127893-200201000-00006"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.05.005"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.07015"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04309.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(02)00053-9"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90337-9"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(93)90178-2"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8249-x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.10.015"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2466"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01660"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2010.07.006"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181c84a9a"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00238-5"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00100-9"}],"container-title":["Journal of the Peripheral Nervous System"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjns5.12032","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjns5.12032","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jns5.12032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T16:18:35Z","timestamp":1696263515000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jns5.12032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":51,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1111\/jns5.12032"],"URL":"https:\/\/doi.org\/10.1111\/jns5.12032","archive":["Portico"],"relation":{},"ISSN":["1085-9489","1529-8027"],"issn-type":[{"value":"1085-9489","type":"print"},{"value":"1529-8027","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9]]}}}