Delneste Y, Herbault N, Galea B, Magistrelli G, Bazin I, Bonnefoy J Y, Jeannin P
Centre d'Immunologie Pierre Fabre, Saint-Julien en Genevois, France.
J Immunol. 1999 Sep 15;163(6):3071-5.
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.
我们研究了不同神经肽对人树突状细胞（DC）成熟的影响。从未成熟DC（由单核细胞与IL-4加GM-CSF培养6天获得）中分别加入生长抑素、P物质或血管活性肠肽（VIP）。在这些神经肽中，只有VIP能诱导一部分DC群体产生生物活性IL-12并使CD83重新表达，其效应分别在100 nM和10 nM时显著。VIP的这些效应呈剂量依赖性，不受多粘菌素B影响，并部分被VIP受体拮抗剂阻断。虽然单独使用VIP的效应仍然有限，但它能与TNF-α协同诱导DC成熟。在存在次优浓度的TNF-α（其本身对DC无明显作用）时，VIP能诱导产生高水平的生物活性IL-12，几乎所有DC群体上CD83的重新表达（其效应分别在10 nM和0.1 nM时显著），以及多种黏附分子和共刺激分子表达的上调。此外，暴露于VIP加次优浓度TNF-α的DC在刺激同种异体T细胞增殖方面与用最佳浓度TNF-α处理获得的成熟DC一样有效。我们的数据表明，在炎症部位，VIP可能与促炎介质如TNF-α协同作用以诱导DC成熟。
