title: Angiogenesis mediated by toll-like receptor 4 in ischemic neural tissue.
abstract: OBJECTIVE
  Activation of the immune system via toll-like receptors (TLRs) is implicated in atherosclerosis, microvascular complications, and angiogenesis. However, the involvement of TLRs in inflammation-associated angiogenesis in ischemic neural tissue has not been investigated. The goal of this study is to determine the role of TLR4 signaling in oxygen-induced neovascularization in retina, a neural tissue.
  
  
  RESULTS
  In oxygen-induced retinopathy model, we found that retinal neovascularization was significantly attenuated in TLR4(-/-) mice. The further study revealed that the absence of TLR4 led to downregulation of proinflammatory factors in association with the attenuated activation of glia in the ischemic retina, which was also associated with reduced expression of high-mobility group box-1, an endogenous ligand for TLR4. The application of high-mobility group box-1 to the ischemic retina promoted the production of proinflammatory factors in wild-type but not TLR4(-/-) mice. High-mobility group box-1 treatment in vitro also significantly promoted the production of proinflammatory factors in retinal glial cells from wild-type mice, but much less from TLR4(-/-) mice.
  
  
  CONCLUSIONS
  Our results suggest that the release of high-mobility group box-1 in ischemic neural tissue initiates TLR4-dependent responses that contribute to neovascularization. These findings represented a previously unrecognized effect of TLR4 on angiogenesis in association with the activation of glia in ischemic neural tissue.
authors.affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P.R.China, 510060.
authors.forename: Chang
authors.initials: C
authors.lastname: He
authors.forename: Yuying
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.forename: Shao-Bo
authors.initials: SB
authors.lastname: Su
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xialin
authors.initials: X
authors.lastname: Liu
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000008:administration & dosage / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D058449:Intravitreal Injections; D007511:Ischemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D015861:Retinal Neovascularization / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D042501:Angiogenic Proteins; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4