Interleukin-32 expression induced by hepatitis B virus protein X is mediated through activation of NF-κB

Mol Immunol. 2011 Jul;48(12-13):1573-7. doi: 10.1016/j.molimm.2011.03.012. Epub 2011 Apr 8.

Abstract

HBV replicates noncytopathically in hepatocytes, but HBV or proteins encoded by HBV genome could induce cytokines, chemokines expression by hepatocytes. Moreover, liver damage in patients with HBV infection is immune-mediated and cytokines play important roles in immune-mediated liver damage after HBV infection. Interleukin-32 (IL-32) is a proinflammatory cytokine and plays a critical role in inflammation. However, the role of HBV in IL-32 expression remains unclear. In the present study, we demonstrate that hepatitis B virus protein X (HBx) increases IL-32 expression through the promoter of IL-32 at positions from -746 to +25 and in a dose-dependent manner. Furthermore, we demonstrate that increase of NF-κB subunits p65 and p50 in Huh7 cells also augments IL-32 expression, and the NF-κB inhibitor blocks the effect of HBx on IL-32 induction. These results indicate that NF-κB activation is required for HBx-induced IL-32 expression. In conclusion, IL-32 is induced by HBx in Huh7 cells. Our results suggest that IL-32 might play an important role in inflammatory response after HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Hepatitis B / immunology
  • Hepatitis B virus / metabolism*
  • Hepatocytes / immunology*
  • Hepatocytes / metabolism
  • Humans
  • Interleukins / biosynthesis
  • Interleukins / genetics*
  • Interleukins / immunology
  • NF-kappa B / metabolism*
  • Plasmids
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins

Substances

  • IL32 protein, human
  • Interleukins
  • NF-kappa B
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein