S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Vasoactive intestinal peptide inhibits Toll Like Receptor 3-induced nitric oxide production in Schwann cells and subsequent sensory neuronal cell death in vitro
- Lee, Hyunkyoung; Park, Kyungpyo; Kim, Joong Soo; Lee, Sung Joong
- Issue Date
- Journal of Neuroscience Research 87:171-178
- vasoactive intestinal peptide; Schwann cells; Toll-like receptor 3; nitric oxide; DRG neurons
- We have previously reported that polyinosinic-polycytidylic acids [poly(I:C)], a synthetic toll-like receptor 3 (TLR3) agonist, induce Schwann cell activation, which exerts neurotoxic effects on sensory neurons. In this study, we investigated the effects of vasoactive intestinal peptide (VIP), a neuropeptide implicated in nerve regeneration, on TLR3-induced Schwann cell activation. VIP receptors VPAC1 and VPAC2 were constitutively expressed in rat Schwann cells. VIP pretreatment inhibited TLR3-induced inducible nitric oxide synthase (iNOS) gene expression and NO production in Schwann cells. Studies on the intracellular signal transduction pathways indicate that the VIP effect is mediated by protein kinase A activation. VIP also inhibited the poly(I:C)-induced p38 activation that is responsible for the iNOS gene expression in Schwann cells. Finally, VIP inhibited dorsal rooyt ganglion neuronal cell death caused by NO produced in activated Schwann cells. Taken together, our data suggest that VIP exerts a neuroprotective effect by inhibiting neurotoxic Schwann cell activation. © 2008 Wiley-Liss, Inc.
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