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

• Published in: Molecular and cellular neuroscience Vol. 45; no. 4; pp. 345 - 354
• Main Authors: Kanekar, Shami, Gandham, Mahendra, Lucero, Mary T
• Format: Journal Article
• Language: English
• Published: 01.12.2010
• Subjects: Adenylate cyclase
• ISSN: 1044-7431
• DOI: 10.1016/j.mcn.2010.07.007

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 TNFa. Live slices of neonatal mouse OE were treated with 40ng/ml TNFaAc40nM PACAP for 6h and dying cells were live-labeled with 0.5% propidium iodide. TNFa significantly increased the percentage of dying cells while co-incubation with PACAP prevented cell death. PACAP also prevented TNFa-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 TNFa 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 TNFa 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.