Inhibition of Trauma-Associated Inflammatory Liver Damage by Blocking NF-κB Activity

Abstract

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