Expression of cytokine, chemokine, and adhesion molecules during endothelial cell activation induced by antibodies against dengue virus nonstructural protein 1.
Vascular dysfunction is a hallmark associated with disease onset in dengue hemorrhagic fever and dengue shock syndrome. In addition to direct viral damage, immune responses to dengue virus (DV) infection may also underlie the pathogenesis of disease. We have proposed a mechanism of molecular mimicry in which Abs directed against DV nonstructural protein 1 (NS1) cross-react with endothelial cells and induce damage. In this study, we demonstrated the inflammatory endothelial cell activation induced by anti-DV NS1 via the transcription factor NF-kappaB-regulated pathway. Protein phosphorylation and NF-kappaB activation were observed after anti-DV NS1 stimulation in a human microvascular endothelial cell line-1. The cytokine and chemokine production, including IL-6, IL-8, and MCP-1, but not RANTES, in endothelial cells increased after treatment with anti-DV NS1 Abs. The expression of IL-6, IL-8, and MCP-1 was blocked by the preabsorption of anti-DV NS1 with DV NS1 or by the inhibition of NF-kappaB activation. Furthermore, the increases in both ICAM-1 expression and the ability of human PBMC to adhere to endothelial cells were also observed, and these effects were inhibited by pretreatment with anti-ICAM-1 or anti-MCP-1 Abs. Therefore, in addition to endothelial cell apoptosis, as previously reported, inflammatory activation occurs in endothelial cells after stimulation by anti-DV NS1 Abs. These results suggest the involvement of anti-DV NS1 Abs in the vasculopathy of DV infection.
Lin
Chiou-Feng
CF
Department of Micribiology and Immunology, National Cheng Kung University Medical College, 1 University Road, Tainan 701, Taiwan.
Chiu
Shu-Chen
SC
Hsiao
Yu-Ling
YL
Wan
Shu-Wen
SW
Lei
Huan-Yao
HY
Shiau
Ai-Li
AL
Liu
Hsiao-Sheng
HS
Yeh
Trai-Ming
TM
Chen
Shun-Hua
SH
Liu
Ching-Chuan
CC
Lin
Yee-Shin
YS
D000818:Animals; D000906:Antibodies; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D003716:Dengue Virus / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D018716:Molecular Mimicry; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D017361:Viral Nonstructural Proteins / Q000276:immunology*
D000906:Antibodies; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D017361:Viral Nonstructural Proteins