Skin-specific caspase-1-transgenic mice show cutaneous apoptosis and pre-endotoxin shock condition with a high serum level of IL-18.
J Immunol
; 165(2): 997-1003, 2000 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-10878376
To study the pathophysiological roles of overexpressed caspase-1 (CASP1), originally designated as IL-1 beta-converting enzyme, we generated transgenic mice in which human CASP1 is overexpressed in their keratinocytes. The transgenic mice spontaneously developed recalcitrant dermatitis and skin ulcers, characterized by the presence of massive keratinocyte apoptosis. The skin of the mice contained the active form of human CASP1 and expressed mRNA for caspase-activated DNase, an effector endonuclease responsible for DNA fragmentation. Their skin and sera showed elevated levels of mature IL-18 and IL-1 beta, but not of IFN-gamma. The plasma from these animals induced IFN-gamma production by IL-18-responsive NK cells. Administration of heat-killed Propionibacterium acnes, a potent in vivo type 1 cell inducer, caused IFN-gamma-mediated lethal liver injury in the transgenic mice, which was completely inhibited by treatment with neutralizing anti-IL-18 Ab. These results indicated that in vivo overexpression of CASP1 caused spontaneous apoptotic tissue injury and rendered mice highly susceptible to exogenous type 1 cell-inducing condition in collaboration with endogenously accumulated proinflammatory cytokines.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Choque Séptico
/
Piel
/
Apoptosis
/
Caspasa 1
/
Interleucina-18
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Immunol
Año:
2000
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos