Toll-Like Receptor 9 Signaling Is Critical for Early Experimental Deep Vein Thrombosis Resolution
| Autor: | Joseph F. Baldwin, Steven L. Kunkel, Gilbert R. Upchurch, Cory M. Hogaboam, Jose A. Diaz, Vikram Sood, Catherine E. Luke, K. Barry Deatrick, Mayo Mitsuya, Thomas W. Wakefield, Peter K. Henke, Megan Elfline |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 31:43-49 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— Toll-like receptors (TLR) bridge innate immunity and host responses, including inflammation. Sterile inflammation such as a venous thrombus (V t ) may involve TLR signaling, including TLR9. Methods and Results— TLR9 signaling on thrombus resolution was investigated using a mouse model of stasis V t . V t were significantly larger in TLR9−/− mice compared with wild-type (WT) at 2 and 8 days, despite a 2-fold increase in thrombus polymorphonucleic neutrophils at 2 days and monocytes at 8 days, whereas thrombus collagen and neovascularization was 55% and 37% less, respectively, at 8 days. Coincidently, decreased fibrinogen and increased thrombin-antithrombin complex were observed in TLR9−/− mouse thrombi. Vein wall interferon-α, interleukin-1α, and interleukin-2 were significantly reduced in TLR9−/− mice compared with WT. Thrombus cell death pathway markers were not significantly altered at 2 days, but caspase-1 was reduced in TLR9−/− thrombi at 8 days. MyD88 confers TLR9 intracellular signaling, but MyD88−/− mice had V t resolution similar to that of WT. However, inhibition of the NOTCH ligand δ-like 4 was associated with larger V t . Finally, stimulation with a TLR9 agonist was associated with smaller V t . Conclusion— TLR9 signaling is integral for early and mid-V t resolution through modulation of sterile inflammation, maintaining a TH1 milieu, and effects on the thrombosis pathway. |
| Databáze: | OpenAIRE |
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