title: The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies.
abstract: Antiphospholipid antibodies (APLAs) promote inflammatory and procoagulant responses in endothelial cells and monocytes. Previous studies have shown that MyD88, TRAF6, and NF-kappaB mediate cell activation by APLAs. These intermediates are also used by toll-like receptors (TLRs). We investigated the role of TLRs in the cellular response to APLAs. IgGs were isolated from the plasma of 5 patients with antiphospholipid syndrome along with immunopurified anti-beta2-glycoprotein 1 IgG from a sixth patient. Control IgG was obtained from a pool of healthy donor plasmas negative for APLAs. Wild-type mouse embryonic fibroblasts (EFs) and EFs deficient in TLR1, TLR2, TLR4, or TLR6 were incubated with APLAs, anti-beta2-glycoprotein 1 IgG, or control IgG. On incubation with the patient IgG, but not control IgG, a significant increase in mRNA levels of the inflammatory marker proteins MCP-1, ICAM-1, and IL-6 as well as IL-6 secretion was observed in wild-type EFs, whereas TLR2-deficient EFs did not respond. Responses in TLR1- and TLR6-deficient EFs were decreased and those in TLR4-deficient EFs comparable to those in wild-type EFs. Overexpression of human TLR2 in the TLR2-deficient EFs restituted the response to patient IgG. Our results imply that TLR2 plays a role in mouse fibroblast activation by APLAs.
authors.affiliation: Division of Angiology and Hemostasis, University Hospital, Faculty of Medicine, Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Satta
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dunoyer-Geindre
authors.forename: Guido
authors.initials: G
authors.lastname: Reber
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fish
authors.forename: Francoise
authors.initials: F
authors.lastname: Boehlen
authors.forename: Egbert K O
authors.initials: EK
authors.lastname: Kruithof
authors.forename: Philippe
authors.initials: P
authors.lastname: de Moerloose
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid; D015415:Biomarkers / Q000097:blood; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000502:physiology*; D053482:beta 2-Glycoprotein I / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers; D007074:Immunoglobulin G; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D053482:beta 2-Glycoprotein I