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Published on: January 22, 2019
Inhibition of constitutive TNF production is associated with PACAP-mediated differentiation in PC12 cells
Destiny-Love Manecka1, Vincent Lelièvre2, Youssef Anouar1
1Inserm, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan, France; Institute for Research and Innovation in Biomedicine, Normandy University, University of Rouen, Mont-Saint-Aignan, France.
Abstract:
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.
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