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Mucosal Immunol. 2017 Mar;10(2):332-340. doi: 10.1038/mi.2016.51. Epub 2016 Jun 8.

Vasoactive intestinal peptide dampens formyl-peptide-induced ROS production and inflammation by targeting a MAPK-p47phox phosphorylation pathway in monocytes.

Chedid P1,2,3, Boussetta T1,2,3, Dang PM1,2,3, Belambri SA1,2,3, Marzaioli V1,2,3, Fasseau M1, Walker F1,2,3,4, Couvineau A1,2,3, El-Benna J1,2,3, Marie JC1,2,3.

Author information

1
Inserm, U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation (CRI), Paris, France.
2
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
3
Laboratoire d'Excellence Inflamex, Faculté de Médecine, Site Xavier Bichat, Paris, France.
4
Service d'Anatomie et Cytologie Pathologique, Hopital Xavier Bichat, Paris, France.

Abstract

Reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase (NOX2) are required for microbial clearance; however, when produced in excess they exacerbate inflammatory response and injure surrounding tissues. NOX2 is a multicomponent enzyme composed of membrane-associated cytochrome b588 and cytosolic components p47phox, p67phox, p40phox, and rac1/2. We investigated whether vasoactive intestinal peptide (VIP), an endogenous immune-modulatory peptide, could affect ROS production by NOX2 in primary human phagocytes. VIP did not modulate basal ROS production by phagocytes, but it inhibited monocyte and not neutrophil ROS production in response to the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF). The action of VIP was essentially mediated by high-affinity G-protein coupled receptors VPAC1 as its specific agonist, [ALA11,22,28]VIP, mimicked VIP-inhibitory effect, whereas the specific VPAC1 antagonist, PG97-269, blunted VIP action. Further, we showed that VIP inhibited fMLF-induced phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2), p38MAPK (p38 mitogen-activated protein kinase) pathways, and phosphorylation of p47phox on Ser345 residue. Also, VIP exerted an anti-inflammatory effect in a model of carrageenan-induced inflammation in rats. We thus found that VIP exerts anti-inflammatory effects by inhibiting the "MAPK-p47phox phosphorylation-NOX2 activation" axis. These data suggest that VIP acts as a natural anti-inflammatory agent of the mucosal system and its analogs could be novel anti-inflammatory molecules.

PMID:
27271317
DOI:
10.1038/mi.2016.51
[Indexed for MEDLINE]

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