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-κB transcription factor, and that PACAP rapidly inhibits TNF expression and secretion. The inhibition occurs through suppression of RelB subunit of NF-κB, and is likely to prevent the deleterious effects of the cytokine on survival and neurite outgrowth during PC12 cell differentiation.