Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori.
OBJECTIVE
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.
Hase
Koji
K
Department of Medicine, University of California at san Diego, La Jolla, 92093, USA.
Murakami
Masamoto
M
Iimura
Mitsutoshi
M
Cole
Sheri P
SP
Horibe
Yoshimune
Y
Ohtake
Takaaki
T
Obonyo
Marygorret
M
Gallo
Richard L
RL
Eckmann
Lars
L
Kagnoff
Martin F
MF
D000230:Adenocarcinoma / Q000276:immunology; D000236:Adenoma / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D054804:Cathelicidins; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D011127:Polyps / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000276:immunology
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D012333:RNA, Messenger