Tumor necrosis factor alpha induces the expression of the nuclear protein p8 via a novel NFκB 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 TNF alpha 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 NFKB motif has been described, we further tested whether TNF alpha stimulates p8 expression via activation of NFKB. We characterized the TNF alpha-induced binding of NFKB to this motif. We show that the TNF alpha-induced NFKB pathway contributes to the induction of p8 during pancreatitis and LPS-induced inflammation.