Vasoactive intestinal peptide synergizes with TNF-alpha in inducing human dendritic cell maturation.
We investigated the effects of different neuropeptides on human dendritic cells (DC) maturation. Immature DC, derived from monocytes cultured for 6 days with IL-4 plus GM-CSF, have been exposed to somatostatin, substance P, or vasoactive intestinal peptide (VIP). Among these neuropeptides, only VIP induces the production of bioactive IL-12 and the neoexpression of CD83 on a fraction of the DC population, with an effect significant at 100 and 10 nM, respectively. These effects of VIP are dose-dependent, unaffected by polymixin B, and partly prevented by a VIP receptor antagonist. Although the effects of VIP alone remain modest, it synergizes with TNF-alpha to induce DC maturation. In the presence of a suboptimal concentration of TNF-alpha, which has no detectable effect on DC by itself, VIP induces the production of high levels of bioactive IL-12, the neoexpression of CD83 on almost all the DC population (with an effect significant at 10 and 0.1 nM, respectively), and the up-regulation of various adhesion and costimulatory molecule expression. Moreover, DC exposed to VIP plus a suboptimal concentration of TNF-alpha are as potent as mature DC obtained by treatment with an optimal concentration of TNF-alpha in stimulating allogenic T cell proliferation. Our data suggest that, in inflammatory sites, VIP may cooperate with proinflammatory mediators, such as TNF-alpha, to induce DC maturation.
Delneste
Y
Y
Centre d'Immunologie Pierre Fabre, Saint-Julien en Genevois, France.
Herbault
N
N
Galea
B
B
Magistrelli
G
G
Bazin
I
I
Bonnefoy
J Y
JY
Jeannin
P
P
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D014660:Vasoactive Intestinal Peptide; D000097802:CD83 Antigen