Vasoactive intestinal peptide inhibits IL-8 production in human monocytes

被引:32
作者
Delgado, M [1 ]
Ganea, D
机构
[1] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA
[2] Univ Complutense Madrid, Fac Biol, Dept Biol Celular, E-28040 Madrid, Spain
关键词
neuroimmunology; neuropeptides; monocytes; chemokines; inflammation; chemotaxis;
D O I
10.1016/S0006-291X(03)00059-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vasoactive intestinal peptide (VIP), a neuropeptide present in the lymphoid microenvironment, acts as a potent anti-inflammatory agent that inhibits the function of activated macrophages. VIP was shown to inhibit IL-6, TNFalpha, IL-12, chemokine, and nitric oxide production in endotoxin-activated macrophages. The present study reports the effect of VIP on IL-8 production by stimulated human monocytes. VIP inhibits IL-8 production in a dose- and time-dependent manner at the mRNA level. The specific VPAC1 receptor mediates the inhibitory effect of VIP. Two transduction pathways appear to be involved, a major cAMP-independent pathway and a secondary cAMP-dependent pathway. Of obvious physiological significance is the fact that VIP, presumably through the inhibition of IL-8 production, dramatically reduces the monocyte-induced neutrophil chemotaxis, an important event in the pathogenesis of several inflammatory and autoimmune disorders. These findings support the proposed role of VIP as a key endogenous anti-inflammatory agent and describe a novel mechanism, i.e., the inhibition of the production of monocyte-derived IL-8. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:825 / 832
页数:8
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