Tumor necrosis factor alpha induces the expression of the nuclear protein p8 via a novel NF kappaB binding site within the promoter.

p8 is a widely expressed HMG-I/Y-like transcription factor which is involved in regulating cell proliferation and tissue stress. Several studies describe a strong upregulation of p8 expression during inflammatory processes like pancreatitis and LPS-induced sepsis. Here we demonstrate that TNFalpha, which is an important inducer of innate defence against gram-negative bacteria, significantly stimulates p8 protein production in H4IIE rat hepatoma cells within 2 hours. Since a putative NF kappaB motif has been described, we further tested whether TNFalpha stimulates p8 expression via activation of NF kappaB. We characterized the TNFalpha-induced binding of NF kappaB to this motif. We show that the TNFalpha-induced NF kappaB pathway contributes to the induction of p8 during pancreatitis and LPS-induced inflammation.