Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori.
Gastroenterology
; 125(6): 1613-25, 2003 Dec.
Article
en En
| MEDLINE
| ID: mdl-14724813
ABSTRACT
BACKGROUND & AIMS:
LL-37/human cationic antimicrobial peptide 18 (hCAP18) is a human cathelicidin with broad-spectrum antimicrobial, lipopolysaccharide binding, and chemotactic activities. This study examined the role of LL-37/hCAP18 in gastric innate immune defense by characterizing its constitutive and regulated expression by human gastric mucosa and its bactericidal activity against the gastric pathogen Helicobacter pylori.METHODS:
LL-37/hCAP18 messenger RNA expression in normal and H. pylori -infected gastric mucosa and gastric epithelial cells was determined by in situ hybridization, real-time polymerase chain reaction, immunostaining, and immunoblot analysis. Bactericidal activity was measured by using a colony-forming unit assay.RESULTS:
LL-37/hCAP18 messenger RNA and protein were expressed in a distinct distribution by surface epithelial cells as well as chief and parietal cells in the fundic glands of normal gastric mucosa. LL-37/hCAP18 was significantly increased in the epithelium and gastric secretions of H. pylori -infected patients, but not in individuals with non-H. pylori -induced gastric inflammation. Infection of cultured gastric epithelial cells with a wild-type but not an isogenic Delta cagE mutant strain of H. pylori increased LL-37/hCAP18 expression, indicating that H. pylori -induced regulation of LL-37/hCAP18 production required an intact type IV secretion system. LL-37, the C-terminal peptide of LL-37/hCAP18, alone or in synergy with human beta-defensin 1, was bactericidal for several H. pylori strains.CONCLUSIONS:
These data indicate that H. pylori up-regulates production of LL-37/hCAP18 by gastric epithelium and suggest this cathelicidin contributes to determining the balance between host mucosal defense and H. pylori survival mechanisms that govern chronic infection with this gastric pathogen.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Helicobacter pylori
/
Infecciones por Helicobacter
/
Péptidos Catiónicos Antimicrobianos
/
Mucosa Gástrica
Límite:
Humans
Idioma:
En
Revista:
Gastroenterology
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos