Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock

被引：0

作者：

Delgado, M ^{[1
]}

Gomariz, RP ^{[1
]}

Martinez, C ^{[1
]}

Abad, C ^{[1
]}

Leceta, J ^{[1
]}

机构：

[1] Univ Complutense Madrid, Fac Biol, Dept Biol Celular, E-28040 Madrid, Spain

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2000年 / 30卷 / 11期

关键词：

neuroimmunomodulation; macrophage; sepsis; inflammation; VPAC agonist;

D O I：

10.1002/1521-4141(200011)30:11<3236::AID-IMMU3236>3.0.CO;2-L

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Vasoactive intestinal peptide (VIP) is a neuropeptide that can modulate several immune aspects. Previous reports showed that VIP attenuates the deleterious consequences of septic shock by inhibiting the production of pro-inflammatory agents and stimulating the production of anti-inflammatory cytokines in activated macrophages. In this study, by using selective VIP agonists, we investigated the differential involvement of the VIP receptors in the anti-inflammatory role of VIP. Both the type 1 VIP receptor (VPAC1) agonist, [K-15, R-16, L-27] VIP [1-7]-GRF [8-27], and the type 2 VIP receptor (VPAC2) agonist, Ro25-1553, protected mice from lethal endotoxemia by inhibiting the macrophage-derived pro-inflammatory mediators IL-6, TNF-alpha, IL-12 and NO, and by stimulating the production of the anti-inflammatory cytokine IL-10. In addition, both VIP and VPAC1 agonist, but not the VPAC2 agonist, reduced in vitro and in vivo the expression of the co-stimulatory B7.1/B7.2 molecules, and the subsequent stimulatory activity for T helper cells in stimulated macrophages. The higher effectiveness of the VPAC1 agonist compared with the VPAC2 agonist suggests that VPAC1 is the major mediator of the anti-inflammatory action of VIP. Since VIP and the two agonists appear to affect multiple cytokines and inflammatory factors, they might provide a more efficient therapeutical alternative to the use of specific cytokine antibodies or antagonists.

引用

页码：3236 / 3246

页数：11

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