Activation of Vascular Endothelial Growth Factor Receptor-3 in Macrophages Restrains TLR4-NF-kappa B Signaling and Protects against Endotoxin Shock

	Activation of Vascular Endothelial Growth Factor Receptor-3 in Macrophages Restrains TLR4-NF-kappa B Signaling and Protects against Endotoxin Shock
	Zhang, YB; Lu, Y; Ma, L; Cao, XD; Xiao, J; Chen, JX; Jiao, SZ; Gao, YZ; Liu, C; Duan, ZJ
刊名	IMMUNITY
	2014
卷号	40 期号:4 页码:501-514
通讯作者	Wei, B (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,binweiwhy@gmail.com ; hongyanwang@sibcb.ac.cn
英文摘要	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-kappa B 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.
学科主题	Immunology
类目[WOS]	Immunology
关键词[WOS]	PHOSPHOINOSITIDE 3-KINASE P110-DELTA ; NEGATIVE REGULATION ; LYMPHATIC VESSELS ; FOXP3 EXPRESSION ; SEVERE SEPSIS ; CUTTING EDGE ; CELLS ; LYMPHANGIOGENESIS ; ANGIOGENESIS ; VEGF
收录类别	SCI
语种	英语
WOS记录号	WOS:000334849400009
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/176]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, YB,Lu, Y,Ma, L,et al. Activation of Vascular Endothelial Growth Factor Receptor-3 in Macrophages Restrains TLR4-NF-kappa B Signaling and Protects against Endotoxin Shock[J]. IMMUNITY,2014,40(4):501-514.
APA	Zhang, YB.,Lu, Y.,Ma, L.,Cao, XD.,Xiao, J.,...&Wang, HY.(2014).Activation of Vascular Endothelial Growth Factor Receptor-3 in Macrophages Restrains TLR4-NF-kappa B Signaling and Protects against Endotoxin Shock.IMMUNITY,40(4),501-514.
MLA	Zhang, YB,et al."Activation of Vascular Endothelial Growth Factor Receptor-3 in Macrophages Restrains TLR4-NF-kappa B Signaling and Protects against Endotoxin Shock".IMMUNITY 40.4(2014):501-514.