Regulation of Pseudomonas aeruginosa corneal infection in IL-1 beta converting enzyme (ICE, caspase-1) deficient mice.
Curr Eye Res
; 29(4-5): 225-33, 2004.
Article
em En
| MEDLINE
| ID: mdl-15590467
ABSTRACT
PURPOSE:
Antibody neutralization studies have shown that in Pseudomonas aeruginosa corneal infection, IL-1 beta is critical to regulation of the host inflammatory response, but mechanisms remain undetermined. To elucidate these mechanisms, caspase-1 knockout (ICE(-/-)) mice, that do not release mature IL-1 beta after endotoxin challenge, were tested.METHODS:
Clinical scores, MPO activity (for PMN quantitation), bacterial plate count, semiquantitative RT-PCR, ELISA and TUNEL staining were used to characterize the inflammatory response after infection in knockout and C57BL/6 (B6) wild type mice.RESULTS:
Clinical scores were significantly reduced in ICE(-/-) vs. B6 mice at 3, 5 and 7 days postinfection (p.i.). The decreased inflammatory response of ICE(-/-) mice was striking at 1 day p.i., and bacterial load also was significantly reduced in the cornea of the knockout mice at 3-7 days p.i. Knockout mice exhibited significantly increased mRNA and protein levels for IL-1Ra, the physiological regulator of IL-1 activity, and in addition, a significant increase in the number of apoptotic cells were quantitated in the corneal epithelium of ICE(-/-) vs. B6 mice at 1 day p.i.CONCLUSIONS:
These data provide evidence that bacterial infection in the cornea of ICE(-/-) mice induces a reduced inflammatory response by reduction in PMN and cytokines and chemokines that attract these cells to the cornea; enhanced apoptotic cell death in the infected epithelium; and increased IL-1Ra levels. The data also confirm the importance of IL-1 regulation in this model and suggest that ICE inhibition may be an attractive ancillary therapeutic strategy to control the host response to this pathogen.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Infecções Oculares Bacterianas
/
Úlcera da Córnea
/
Caspase 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Curr Eye Res
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos