| First Author | Zhang Y | Year | 2014 |
| Journal | Immunity | Volume | 40 |
| Issue | 4 | Pages | 501-14 |
| PubMed ID | 24656836 | Mgi Jnum | J:209991 |
| Mgi Id | MGI:5569210 | Doi | 10.1016/j.immuni.2014.01.013 |
| Citation | Zhang Y, et al. (2014) Activation of vascular endothelial growth factor receptor-3 in macrophages restrains TLR4-NF-kappaB signaling and protects against endotoxin shock. Immunity 40(4):501-14 |
| abstractText | Toll-like receptors (TLRs) are critical in mediating innate immune responses against infections. However, uncontrolled TLR-triggered inflammation is associated with endotoxin shock. To better understand the homeostatic mechanisms induced by TLR4 signaling, we screened a group of key cytokines, chemokines, growth factors, and their receptors for bacteria- or LPS-induced expression. The surface vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C were upregulated in macrophages. VEGFR-3 ligation by VEGF-C significantly attenuated proinflammatory cytokine production. Notably, ablation of the ligand-binding domain or tyrosine kinase activity of VEGFR-3 rendered mice more sensitive to septic shock. VEGFR-3 restrained TLR4-NF-kappaB activation by regulating the PI3-kinase-Akt signaling pathway and SOCS1 expression. Aside from targeting lymphatic vessels, we suggest a key role of VEGFR-3 on macrophages to prevent infections that is complicated with lymphoedema. Thus, VEGFR-3-VEGF-C signaling represents a "self-control" mechanism during antibacterial innate immunity. |
