Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway

Virus Res. 2007 Sep;128(1-2):1-8. doi: 10.1016/j.virusres.2007.02.007. Epub 2007 May 25.

Abstract

The clinical picture of severe acute respiratory syndrome (SARS) is characterized by an over-exuberant immune response with lung lymphomononuclear cells infilteration and proliferation that may account for tissue damage more than the direct effect of viral replication. To understand how cells response in the early stage of virus-host cell interaction, in this study, a purified recombinant S protein was studied for stimulating murine macrophages (RAW264.7) to produce proinflammatory cytokines (IL-6 and TNF-alpha) and chemokine IL-8. We found that direct induction of IL-6 and TNF-alpha release in the supernatant in a dose-, time-dependent manner and highly spike protein-specific, but no induction of IL-8 was detected. Further experiments showed that IL-6 and TNF-alpha production were dependent on NF-kappaB, which was activated through I-kappaBalpha degradation. These results suggest that SARS-CoV spike protein may play an important role in the pathogenesis of SARS, especially in inflammation and high fever.

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Macrophage Activation
  • Macrophages / immunology*
  • Macrophages / virology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • SARS Virus / genetics
  • SARS Virus / immunology*
  • Spike Glycoprotein, Coronavirus
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism

Substances

  • Interleukin-6
  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • NF-kappa B
  • Spike Glycoprotein, Coronavirus
  • Tumor Necrosis Factor-alpha
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV