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- W4328001085 abstract "Tumor necrosis factor-α (TNF-α) production accompanies CNS insults of all kinds. Because the neuropeptide vasoactive intestinal peptide (VIP) and the structurally related peptide pituitary adenylyl cyclase-activating polypeptide (PACAP) have potent anti-inflammatory effects in the periphery, we investigated whether these effects extend to the CNS. TNF-α mRNA was induced within 2 hr after rat spinal cord transection, and its upregulation was suppressed by a synthetic VIP receptor agonist. Cultured rat microglia were used to examine the mechanisms underlying this inhibition because microglia are the likely source of TNF-α in injured CNS. In culture, increases in TNF-α mRNA resulting from lipopolysaccharide (LPS) stimulation were reduced significantly by 10 −7 m VIP and completely eliminated by PACAP at the same concentration. TNF-α protein levels were reduced 90% by VIP or PACAP at 10 −7 m . An antagonist of VPAC 1 receptors blocked the action of VIP and PACAP, and a PAC 1 antagonist blocked the action of PACAP. A direct demonstration of VIP binding on microglia and the existence of mRNAs for VPAC 1 and PAC 1 (but not VPAC 2 ) receptors argue for a receptor-mediated effect. The action of VIP is cAMP-mediated because (1) activation of cAMP by forskolin mimics the action; (2) PKA inhibition by H89 reverses the neuropeptide-induced inhibition; and (3) the lipophilic neuropeptide mimic, stearyl-norleucine 17 VIP (SNV), which does not use a cAMP-mediated pathway, fails to duplicate the inhibition. We conclude that VIP and PACAP inhibit the production of TNF-α from activated microglia by a cAMP-dependent pathway." @default.
- W4328001085 created "2023-03-22" @default.
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- W4328001085 date "2000-05-15" @default.
- W4328001085 modified "2023-10-18" @default.
- W4328001085 title "Vasoactive Intestinal Peptide and Pituitary Adenylyl Cyclase-Activating Polypeptide Inhibit Tumor Necrosis Factor-α Production in Injured Spinal Cord and in Activated Microglia via a cAMP-Dependent Pathway" @default.
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- W4328001085 doi "https://doi.org/10.1523/jneurosci.20-10-03622.2000" @default.
- W4328001085 hasPublicationYear "2000" @default.
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