Caspase-4: A Therapeutic Target for Peptic Ulcer Disease.
Immunohorizons
; 4(10): 627-633, 2020 10 12.
Article
en En
| MEDLINE
| ID: mdl-33046484
ABSTRACT
Peptic ulcers are caused by the interaction between bacterial and host factors. This study demonstrates enhanced expression of caspase-4 in peptic ulcer patient biopsies, indicating that pyroptosis and noncanonical inflammasome activity may be processes involved in peptic ulcer disease. We show that primary murine macrophages infected with Helicobacter pylori upregulate caspase-11 (the ortholog of human caspase-4), activate caspase-1, and secrete IL-1ß. We demonstrate that misoprostol (a stable PGE1 analogue) decreased IL-1ß secretion and delayed lethality in vivo in a murine peritonitis model. PGE2 was shown to inhibit caspase-11-driven pyroptosis and IL-1ß secretion in macrophages. Overall, we provide evidence for a pathological role of caspase-4/11 in peptic ulcer disease and propose that targeting caspase-4 or inhibiting pyroptosis may have therapeutic potential in the management of peptic ulcers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Úlcera Péptica
/
Helicobacter pylori
/
Infecciones por Helicobacter
/
Caspasas Iniciadoras
/
Interleucina-1beta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Immunohorizons
Año:
2020
Tipo del documento:
Article