title: Brief Report: Endothelial-Specific X-Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor-Induced Leukocyte Recruitment and Vasculitis.
abstract: OBJECTIVE
  Endothelial cell activation by tumor necrosis factor (TNF) and associated leukocyte infiltration are hallmarks of vasculitis. The aim of this study was to investigate the potential role of the cellular stress-associated endothelial X-box binding protein 1 (XBP-1) transcription factor in TNF-induced endothelial cell inflammation and vasculitis.
  
  
  METHODS
  Mice with an endothelial cell-specific XBP-1 deficiency were used in a modified local Shwartzman reaction (LSR) model of TNF-induced small vessel vasculitis. To address the contribution of XBP-1 to the TNF-mediated inflammatory response in endothelial cells, we examined the activation of XBP-1 expression by TNF as well as the effect of XBP-1 knockdown in endothelial cells on TNF-induced signaling, proinflammatory gene expression, and leukocyte-endothelial cell adhesion.
  
  
  RESULTS
  The active spliced form of XBP-1 in endothelial cells was triggered by TNF. In addition, endothelial XBP-1 contributed to the sustained TNF-triggered NF-κB-dependent transcriptional activation of proinflammatory molecules, which was associated with leukocyte-endothelial cell adhesion. In the LSR model, endothelial cell-specific XBP-1-deficient mice displayed significantly less vascular damage, accompanied by reduced perivascular neutrophil infiltration, as compared with wild-type mice.
  
  
  CONCLUSIONS
  Endothelial XBP-1 is activated by TNF and regulates leukocyte-endothelial cell adhesion in vitro as well as neutrophil infiltration and vascular damage in murine vasculitis.
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Ziogas
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Muders
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Matina
authors.initials: M
authors.lastname: Economopoulou
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Sprott
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Grossklaus
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siegert
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Baretton
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D000071701:Regulatory Factor X Transcription Factors; D012790:Shwartzman Phenomenon / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014657:Vasculitis / Q000235:genetics* / Q000276:immunology; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse