Vasoactive intestinal peptide inhibits IL-8 production in human monocytes.
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.
Delgado
Mario
M
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA. mariodm@bio.ucm.es
Ganea
Doina
D
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D015398:Signal Transduction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009479:Neuropeptides; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP