Anti-vascular permeability of the cleaved reactive center loop within the carboxyl-terminal domain of C1 inhibitor
| Autor: | Gao Chen, Meng yuan Liu, Dong-xu Liu, Hai mou Zhang, Zhi de Cheng, Gang jian Qin, Gang Liang |
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| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Umbilical Veins Amino Acid Motifs Immunology Vascular Cell Adhesion Molecule-1 Vascular permeability Serpin C1-inhibitor Capillary Permeability Mice Cell Adhesion Animals Humans Cell adhesion Molecular Biology Reactive center Cells Cultured Cytoskeleton Mice Inbred BALB C biology NF-kappa B I-Kappa-B Kinase Endothelial Cells Cell biology Endothelial stem cell biology.protein I-kappa B Proteins Human umbilical vein endothelial cell Endothelium Vascular Complement C1 Inhibitor Protein |
| Zdroj: | Molecular Immunology. 45:1743-1751 |
| ISSN: | 0161-5890 |
| Popis: | C1 inhibitor (C1INH), a member of the serine proteinase inhibitor (serpin) family, functions as an inhibitor of the complement and contact systems. Cleavage of the reactive center loop (RCL) within the carboxyl-terminal domain of C1INH (iC1INH), lacking of serpin function, induces a conformational change in the molecule. Our previous data demonstrated that active, intact C1INH prevents vascular permeability induced by gram-negative bacterial lipopolysaccharide (LPS). In this study, we investigate the role of RCL-cleaved, inactive C1INH (iC1INH) in vascular endothelial activation. In the cultured primary human umbilical vein endothelial cell (HUVEC) monolayer, iC1INH blocked LPS-induced cell injury by evaluated as transendothelial flux, cell detachment, and cytoskeletal disorganization. LPS-induced upregulation of vascular cell adhesion molecule-1 (VCAM-1) could be suppressed by treatment with iC1INH. Studies exploring the underlying mechanism of iC1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-kappaB activation and nuclear translocation in an I kappa B alpha-dependent manner. The inhibitory effect was associated with stabilization of the NF-kappaB inhibitor I kappa B and reduction of inhibitor I kappa B kinase activity. In the model of endotoxin-induced mice, increased plasma leakage in local abdominal skin in response to LPS was reversed by treatment with iC1INH. Furthermore, systemic administration of LPS to mice resulted in increased microvascular permeability in multiple organs, which was reduced by iC1INH. These data provide evidence that iC1INH has an anti-vascular permeability independent on the serpin function. |
| Databáze: | OpenAIRE |
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