The vasoactive peptide maxadilan from sand fly saliva inhibits TNF-alpha and induces IL-6 by mouse macrophages through interaction with the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor.
J Immunol
; 160(4): 1811-6, 1998 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-9469441
ABSTRACT
Maxadilan is a vasodilatory peptide encoded by a gene cloned from Lutzomyia longipalpis salivary glands. In this study we investigated the effects of maxadilan on macrophage functions. Maxadilan treatment of LPS-stimulated BALB/c macrophages inhibited TNF-alpha release but increased IL-6. Further, it also induced IL-6 release in a dose-dependent manner from unstimulated macrophages. Maxadilan increased production of PGE2, and the inhibition of TNF-alpha was completely abrogated by indomethacin. Others have recently shown that maxadilan is a selective agonist of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor. Treatment with the receptor antagonist PACAP 6-38 blocked maxadilan activities on macrophages. The natural endogenous ligand, PACAP 38, had the same effects as maxadilan on TNF-alpha and IL-6 production. Finally, in a dose- and time-dependent fashion, maxadilan induced the intracellular accumulation of cAMP in macrophages. Taken together, the results presented here indicate a modulatory effect of ligands of PACAP type I receptor on cytokine production by macrophages and suggest that activation of this receptor, with the subsequent elevation of intracellular cAMP in macrophages, could participate in a negative-feedback mechanism that controls certain inflammatory responses.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas e Peptídeos Salivares
/
Neuropeptídeos
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Receptores do Hormônio Hipofisário
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Interleucina-6
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Fator de Necrose Tumoral alfa
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Proteínas de Insetos
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Macrófagos
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos