PACAP protects against TNFα-induced cell death in olfactory epithelium and olfactory placodal cell lines.

Molecular and Cellular Neurosciences
Shami KanekarMary T Lucero

Abstract

In mouse olfactory epithelium (OE), pituitary adenylate cyclase-activating peptide (PACAP) protects against axotomy-induced apoptosis. We used mouse OE to determine whether PACAP protects neurons during exposure to the inflammatory cytokine TNFα. Live slices of neonatal mouse OE were treated with 40 ng/ml TNFα ± 40nM PACAP for 6h and dying cells were live-labeled with 0.5% propidium iodide. TNFα significantly increased the percentage of dying cells while co-incubation with PACAP prevented cell death. PACAP also prevented TNFα-mediated cell death in the olfactory placodal (OP) cell lines, OP6 and OP27. Although OP cell lines express all three PACAP receptors (PAC1, VPAC1,VPAC2), PACAP's protection of these cells from TNFα was mimicked by the specific PAC1 receptor agonist maxadilan and abolished by the PAC1 antagonist PACAP6-38. Treatment of OP cell lines with blockers or activators of the PLC and AC/MAPKK pathways revealed that PACAP-mediated protection from TNFα involved both pathways. PACAP may therefore function through PAC1 receptors to protect neurons from cell death during inflammatory cytokine release in vivo as would occur upon viral infection or allergic rhinitis-associated injury.

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Citations

Aug 28, 2016·Journal of Molecular Neuroscience : MN·A VaczyT Atlasz
Apr 20, 2016·Scientific Reports·Adrien FrançoisNicolas Meunier
May 11, 2011·Journal of Neuroendocrinology·M-C LacroixF Renaud
Jan 23, 2016·Journal of Cellular and Molecular Medicine·Xiaoling GuoJiansu Chen
Jan 26, 2021·Frontiers in Cellular and Infection Microbiology·Lynn NazarethJenny A K Ekberg
May 23, 2021·Scientific Reports·Indra N ChoudhuryJenny A K Ekberg

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