title: Novel role of Cdc42 and RalA GTPases in TNF-α mediated secretion of CCL2.
abstract: Transendothelial migration of autoreactive leukocytes into peripheral nerves is an early pathological hallmark of acute inflammatory demyelinating polyneuropathy (AIDP), a North American and European variant of Guillain-Barré Syndrome. Whereas the clinical management of AIDP is currently limited to non-selective immune modulating therapies, recent experimental studies support selective targeting of leukocyte trafficking as a promising alternative therapeutic strategy. Here, using a combination of targeted siRNA knockdown and pharmacological inhibitors, we report a novel role of both Cdc42 and RalA GTPases in facilitating TNF-α mediated CCL2 trafficking and release from immortalized rat peripheral nerve microvascular endoneurial endothelial cells. These findings raise interest in Cdc42 and RalA GTPases as potential therapeutic targets for the management of autoimmune inflammatory peripheral nerve disease.
authors.affiliation: Research Service; Department of Veterans Affairs; Edward Hines Jr. VA Hospital; Hines, IL USA; Neuroscience Institute; Stritch School of Medicine; Loyola University Chicago; Maywood, IL USA; Department of Ophthalmology; Stritch School of Medicine; Loyola University Chicago; Maywood, IL USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Langert
authors.affiliation: Research Service; Department of Veterans Affairs; Edward Hines Jr. VA Hospital; Hines, IL USA; Neuroscience Institute; Stritch School of Medicine; Loyola University Chicago; Maywood, IL USA; Department of Ophthalmology; Stritch School of Medicine; Loyola University Chicago; Maywood, IL USA.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Pervan
authors.affiliation: Research Service; Department of Veterans Affairs; Edward Hines Jr. VA Hospital; Hines, IL USA; Neuroscience Institute; Stritch School of Medicine; Loyola University Chicago; Maywood, IL USA; Department of Ophthalmology; Stritch School of Medicine; Loyola University Chicago; Maywood, IL USA.
authors.forename: Evan B
authors.initials: EB
authors.lastname: Stubbs
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020725:ral GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D001549:Benzamides; D018932:Chemokine CCL2; C102521:GGTI 298; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D019883:Alkyl and Aryl Transferases; C492197:Rala protein, rat; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020725:ral GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Cdc42; GTPase; RalA; endothelial; siRNA