Expression of cytokine, chemokine, and adhesion molecules during endothelial cell activation induced by antibodies against dengue virus nonstructural protein 1

Chiou Feng Lin, Shu Chen Chiu, Yu Ling Hsiao, Shu Wen Wan, Huan Yao Lei, Ai Li Shiau, Hsiao Sheng Liu, Trai Ming Yeh, Shun Hua Chen, Ching Chuan Liu, Yee Shin Lin

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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-κB-regulated pathway. Protein phosphorylation and NF-κB 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-κB 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.

Original languageEnglish
Pages (from-to)395-403
Number of pages9
JournalJournal of Immunology
Volume174
Issue number1
DOIs
Publication statusPublished - 2005 Jan 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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