Alpha1-antitrypsin, old dog, new tricks. Alpha1-antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP.
J Biol Chem
; 282(12): 8573-82, 2007 Mar 23.
Article
en En
| MEDLINE
| ID: mdl-17261591
ABSTRACT
Regulation of serine protease activity is considered to be the sole mechanism for the function of alpha1-antitrypsin (AAT). However, recent reports of the anti-inflammatory effects of AAT are hard to reconcile with this classical mechanism. We discovered that two key activities of AAT in vitro, namely inhibition of endotoxin-stimulated tumor necrosis factor-alpha and enhancement of interleukin-10 in human monocytes, are mediated by an elevation of cAMP and activation of cAMP-dependent protein kinase A. As expected with this type of mechanism, the AAT-mediated rise in cAMP and the impact on endotoxin-stimulated tumor necrosis factor-alpha and interleukin-10 was enhanced when the catabolism of cAMP was blocked by the phosphodiesterase inhibitor rolipram. These effects were still observed with modified forms of AAT lacking protease inhibitor activity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Monocitos
/
Alfa 1-Antitripsina
/
Factor de Necrosis Tumoral alfa
/
Interleucina-10
/
AMP Cíclico
/
Endotoxinas
/
Antiinflamatorios
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2007
Tipo del documento:
Article
País de afiliación:
Suecia