TWEAK enhances E-selectin and ICAM-1 expression, and may contribute to the development of cutaneous vasculitis

PLoS One. 2013;8(2):e56830. doi: 10.1371/journal.pone.0056830. Epub 2013 Feb 15.

Abstract

Our previous work indicated that TWEAK is associated with various types of cutaneous vasculitis (CV). Herein, we investigate the effects of TWEAK on vascular injury and adhesion molecule expression in CV mice. We showed that TWEAK priming in mice induced a local CV. Furthermore, TWEAK priming also increased the extravasation of FITC-BSA, myeloperoxidase activity and the expression of E-selectin and ICAM-1. Conversely, TWEAK blockade ameliorated the LPS-induced vascular damage, leukocyte infiltrates and adhesion molecules expression in LPS-induced CV. In addition, TWEAK treatment of HDMECs up-regulated E-selectin and ICAM-1 expression at both mRNA and protein levels. TWEAK also enhanced the adhesion of PMNs to HDMECs. Finally, western blot data revealed that TWEAK can induce phosphorylation of p38, JNK and ERK in HDMECs. These data suggest that TWEAK acted as an inducer of E-selectin and ICAM-1 expression in CV mice and HDMECs, may contribute to the development of CV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Adhesion / drug effects
  • Cytokine TWEAK
  • E-Selectin / genetics*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Enzyme Activation / drug effects
  • Gene Expression Regulation* / drug effects
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peroxidase / metabolism
  • Reactive Oxygen Species / metabolism
  • Receptors, Tumor Necrosis Factor / blood
  • TWEAK Receptor
  • Tumor Necrosis Factors / blood
  • Tumor Necrosis Factors / immunology
  • Tumor Necrosis Factors / metabolism*
  • Tumor Necrosis Factors / pharmacology
  • Up-Regulation / drug effects
  • Vasculitis, Leukocytoclastic, Cutaneous / chemically induced
  • Vasculitis, Leukocytoclastic, Cutaneous / genetics*
  • Vasculitis, Leukocytoclastic, Cutaneous / metabolism*
  • Vasculitis, Leukocytoclastic, Cutaneous / pathology

Substances

  • Cytokine TWEAK
  • E-Selectin
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor
  • TWEAK Receptor
  • Tnfsf12 protein, mouse
  • Tumor Necrosis Factors
  • Intercellular Adhesion Molecule-1
  • Peroxidase

Grants and funding

This work was supported by Natural Science Foundation of China (NO. 81101198) to TC and NO. 81271752 to Z-PG). URL: http://www.nsfc.gov.cn/Portal0/default152.htm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.