TNF-alpha mediated NF-kappaB activation is constantly extended by transglutaminase 2

Front Biosci (Elite Ed). 2011 Jan 1;3:341-54. doi: 10.2741/e249.

Abstract

Increased levels of transglutaminase 2 (TGase 2) expression have been reported in many inflammatory diseases, as well as in drug resistant cancer cells. Previous reports have shown that TGase 2 is capable of inducing nuclear factor-kappaB (NF-kappaB) activation via depletion of inhibitor of kappaB (I-kappaB)alpha through polymerization in the absence of I-kappaBalpha kinase activation. This raises the question of whether increased expression of TGase 2 can extend NF-kappaB activation mediated by a canonical activation pathway. In the TGase 2-inducible EcR23/TG cell line, TGase 2 over-expression resulted in sustained activation of NF-kappa B in the presence of TNF-alpha, for up to 24 hrs, while in the absence of TGase 2 induction, NF-kappaB activity was restored to basal levels within 6 hrs of TNF-alpha treatment. In mice injected with an adenovirus vector expressing TGase 2, NF-kappaB was constitutively activated for up to 5 days, whereas Adeno/GFP-injected mice exhibited attenuated activation of NF-kappaB in response to TNF-alpha stress. Thus, the presence of increased levels of TGase 2 may exacerbate NF-kappa B activation in inflammatory states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Blotting, Western
  • Cell Line
  • Cystamine / pharmacology
  • Electrophoretic Mobility Shift Assay
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Immunohistochemistry
  • Inflammation / metabolism*
  • Liver / metabolism
  • Mice
  • NF-kappa B / metabolism*
  • Plasmids / genetics
  • Transglutaminases / antagonists & inhibitors
  • Transglutaminases / genetics
  • Transglutaminases / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • transglutaminase 2
  • Transglutaminases
  • GTP-Binding Proteins
  • Cystamine