Suppression of complement regulatory protein C1 inhibitor in vascular endothelial activation by inhibiting vascular cell adhesion molecule-1 action.
Increased expression of adhesion molecules by activated endothelium is a critical feature of vascular inflammation associated with the several diseases such as endotoxin shock and sepsis/septic shock. Our data demonstrated complement regulatory protein C1 inhibitor (C1INH) prevents endothelial cell injury. We hypothesized that C1INH has the ability of an anti-endothelial activation associated with suppression of expression of adhesion molecule(s). C1INH blocked leukocyte adhesion to endothelial cell monolayer in both static assay and flow conditions. In inflammatory condition, C1INH reduced vascular cell adhesion molecule (VCAM-1) expression associated with its cytoplasmic mRNA destabilization and nuclear transcription level. Studies exploring the underlying mechanism of C1INH-mediated suppression in VCAM-1 expression were related to reduction of NF-kappaB activation and nuclear translocation in an IkappaBalpha-dependent manner. The inhibitory effects were associated with reduction of inhibitor IkappaB kinase activity and stabilization of the NF-kappaB inhibitor IkappaB. These findings indicate a novel role for C1INH in inhibition of vascular endothelial activation. These observations could provide the basis for new therapeutic application of C1INH to target inflammatory processes in different pathologic situations.
Zhang
Haimou
H
Center for Infection and Immunity Research, School of Life Sciences, Hubei University, Wuhan, Hubei, PR China.
Qin
Gangjian
G
Liang
Gang
G
Li
Jinan
J
Chiu
Isaac
I
Barrington
Robert A
RA
Liu
Dongxu
D
D002478:Cells, Cultured; D003174:Complement C1 Inactivator Proteins / Q000276:immunology*; D050718:Complement C1 Inhibitor Protein; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D015843:Serpins / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D008070:Lipopolysaccharides; C469952:SERPING1 protein, human; D015843:Serpins; D019010:Vascular Cell Adhesion Molecule-1