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Brief Report: Endothelial-Specific X-Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor-Induced Leukocyte Recruitment and Vasculitis.
- Source :
-
Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2015 Dec; Vol. 67 (12), pp. 3279-85. - Publication Year :
- 2015
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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.<br />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.<br />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.<br />Conclusion: 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.<br /> (© 2015, American College of Rheumatology.)
- Subjects :
- Animals
Cell Adhesion drug effects
Cell Adhesion immunology
DNA-Binding Proteins immunology
Disease Models, Animal
Endothelial Cells drug effects
Endothelial Cells immunology
Leukocytes drug effects
Leukocytes immunology
Leukocytes metabolism
Mice
Mice, Knockout
NF-kappa B drug effects
NF-kappa B immunology
Neutrophil Infiltration drug effects
Neutrophil Infiltration immunology
Regulatory Factor X Transcription Factors
Shwartzman Phenomenon immunology
Transcription Factors immunology
Tumor Necrosis Factor-alpha pharmacology
Vasculitis immunology
X-Box Binding Protein 1
Cell Adhesion genetics
DNA-Binding Proteins genetics
Endothelial Cells metabolism
NF-kappa B metabolism
Neutrophil Infiltration genetics
Shwartzman Phenomenon genetics
Transcription Factors genetics
Vasculitis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2326-5205
- Volume :
- 67
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Arthritis & rheumatology (Hoboken, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 26245636
- Full Text :
- https://doi.org/10.1002/art.39309