Inhibition of trauma-associated inflammatory liver damage by blocking NF-κB activity

Hepatogastroenterology. 2012 Jun;59(116):1174-8. doi: 10.5754/hge11624.

Abstract

Background/aims: NF-κB protein family members act as transcription facts and play a key role in regulating the immune response to infection and inflammatory signals. We proposed to determine the role of NF-κB in the development of trauma-associated liver damage and inflammation.

Methodology: NF-κB DNA-binding activity was inhibited using double-stranded oligodeoxynucleotides (ODN). A total of 288 Wistar rats were randomly divided into four groups: control (C), traumatic inflammation (T), traumatic inflammation plus NF-κB decoy (ODN) and traumatic inflammation plus mutant NF-κB decoy ODN (mODN).

Results: Our data shows that inhibition of NF-κB activation significantly reduces liver tissue damage as evidenced by serum ALT levels and histological changes using both light microscopy and transmission electron microscopy. Furthermore, EMSA results showed that NF-κB activation was reduced in Group ODN rats compared to Group T and Group mODN rats. Expression of TNF-a and IL-6 protein in Group ODN rats were also reduced compared to Group T and Group mODN rats. We demonstrated that NF-κB plays an important role in trauma-associated inflammation and liver tissue damage.

Conclusions: Suppressing NF-κB activation effectively reduces the release of the pro-inflammatory cytokines TNF-a and IL-6 following liver trauma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Inflammation / etiology
  • Inflammation / prevention & control
  • Interleukin-6 / blood
  • Liver / pathology
  • Liver Diseases / etiology*
  • Liver Diseases / prevention & control
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / blood
  • Wounds and Injuries / complications*

Substances

  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Alanine Transaminase