Inhibition of endotoxin-induced macrophage chemokine production by VIP and PACAP in vitro and in vivo.
Arch Physiol Biochem
; 109(4): 377-82, 2001 Oct.
Article
em En
| MEDLINE
| ID: mdl-11935377
ABSTRACT
Inflammatory chemokines recruit immune cells which initiate and maintain the inflammatory response. Although such a response is necessary for the elimination of the antigen, the inflammation has to be eventually resolved. Peptides such as vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), released following antigenic stimulation, contribute to the termination of an inflammatory response primarily by inhibiting the production of proinflammatory cytokines. Here we investigated the effects of VIP and PACAP on chemokine production. We report that VIP and PACAP inhibit the expression of the macrophage-derived CXC chemokines MIP-2 and KC (IL-8), and of the CC chemokines MIP-1a, MIP-1b, MCP-1 and RANTES in vivo and in vitro. The decrease of chemokine gene expression correlates with an inhibitory effect of VIP/PACAP on NFkB binding. In an in vivo model of acute peritonitis, the inhibition of chemokine production by VIP/PACAP leads to a significant reduction in the recruitment of PMNs, macrophages and lymphocytes into the peritoneal cavity. These findings support the proposed role of VIP and PACAP as key endogenous anti-inflammatory agents, and describe a novel mechanism, i.e., the inhibition of the production of macrophage-derived chemokines.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
/
Peptídeo Intestinal Vasoativo
/
Lipopolissacarídeos
/
Macrófagos Peritoneais
/
Quimiocinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arch Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FISIOLOGIA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos