Tumor Necrosis Factor Alpha Induces the Expression of the Nuclear Protein p8 via a Novel NFκB Binding Site within the Promoter

Abstract

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 TNFα, 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 NFκB motif has been described, we further tested whether TNFα stimulates p8 expression via activation of NFκB. We characterized the TNFα-induced binding of NFκB to this motif. We show that the TNFα-induced NFκB pathway contributes to the induction of p8 during pancreatitis and LPS-induced inflammation.

Key words

TNFα - p8 expression - com1 - Nupr1 - NFκB - inflammation

References

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