| First Author | Satta N | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 4 | Pages | 1507-14 |
| PubMed ID | 17082324 | Mgi Jnum | J:144455 |
| Mgi Id | MGI:3830948 | Doi | 10.1182/blood-2005-03-024463 |
| Citation | Satta N, et al. (2007) The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies. Blood 109(4):1507-14 |
| abstractText | 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. |
