Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.
Blood
; 113(10): 2324-35, 2009 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-19104081
ABSTRACT
The processing of pro-interleukin-1beta depends on activation of caspase-1. Controversy has arisen whether Toll-like receptor (TLR) ligands alone can activate caspase-1 for release of interleukin-1beta (IL-1beta). Here we demonstrate that human blood monocytes release processed IL-1beta after a one-time stimulation with either TLR2 or TLR4 ligands, resulting from constitutively activated caspase-1 and release of endogenous adenosine triphosphate. The constitutive activation of caspase-1 depends on the inflammasome components, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and NALP3, but in monocytes caspase-1 activation is uncoupled from pathogen-associated molecular pattern recognition. In contrast, macrophages are unable to process and release IL-1beta solely by TLR ligands and require a second adenosine triphosphate stimulation. We conclude that IL-1beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Monocitos
/
Interleucina-1beta
/
Inflamación
/
Macrófagos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Blood
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos