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• W4313376917 endingPage "4696" @default.
• W4313376917 startingPage "4685" @default.
• W4313376917 abstract "Abstract High-output nitric oxide (NO) production from activated macrophages, resulting from the induction of inducible NO synthase (iNOS) expression, represents a major mechanism for macrophage cytotoxicity against pathogens. However, despite its beneficial role in host defense, sustained high-output NO production was also implicated in a variety of acute inflammatory diseases and autoimmune diseases. Therefore, the down-regulation of iNOS expression during an inflammatory process plays a significant physiological role. This study examines the role of two immunomodulatory neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), on NO production by LPS-, IFN-γ-, and LPS/IFN-γ-stimulated peritoneal macrophages and the Raw 264.7 cell line. Both VIP and PACAP inhibit NO production in a dose- and time-dependent manner by reducing iNOS expression at protein and mRNA level. VPAC1, the type 1 VIP receptor, which is constitutively expressed in macrophages, and to a lesser degree VPAC2, the type 2 VIP receptor, which is induced upon macrophage activation, mediate the effect of VIP/PACAP. VIP/PACAP inhibit iNOS expression and activity both in vivo and in vitro. Two transduction pathways appear to be involved, a cAMP-dependent pathway that preferentially inhibits IFN regulatory factor-1 transactivation and a cAMP-independent pathway that blocks NF-κB binding to the iNOS promoter. The down-regulation of iNOS expression, together with previously reported inhibitory effects on the production of the proinflammatory cytokines IL-6, TNF-α, and IL-12, and the stimulation of the anti-inflammatory IL-10, define VIP and PACAP as “macrophage deactivating factors” with significant physiological relevance." @default.
• W4313376917 created "2023-01-06" @default.
• W4313376917 creator A5017574088 @default.
• W4313376917 creator A5019422306 @default.
• W4313376917 creator A5020844761 @default.
• W4313376917 creator A5045927271 @default.
• W4313376917 date "1999-04-15" @default.
• W4313376917 modified "2023-10-14" @default.
• W4313376917 title "Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide Prevent Inducible Nitric Oxide Synthase Transcription in Macrophages by Inhibiting NF-κB and IFN Regulatory Factor 1 Activation" @default.
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• W4313376917 doi "https://doi.org/10.4049/jimmunol.162.8.4685" @default.
• W4313376917 hasPublicationYear "1999" @default.
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