Inhibition of constitutive TNF production is associated with PACAP-mediated differentiation in PC12 cells

The pituitary adenylate cyclase-activating polypeptide (PACAP) is a trophic neuropeptide that promotes cell survival and neuritogenesis in the central and peripheral nervous system. Our previous transcriptomic studies revealed the down-regulation of the cytokine tumor necrosis factor (TNF) during PACAP-induced PC12 cell differentiation. Here we show that TNF is constitutively expressed in PC12 cells in a manner dependent on NF-kappa B transcription factor, and that PACAP rapidly inhibits TNF expression and secretion. The inhibition occurs through suppression of RelB subunit of NF-kappa B, and is likely to prevent the deleterious effects of the cytokine on survival and neurite outgrowth during PC12 cell differentiation. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.