Expression of beta-defensin 4 is increased in human gastritis.
BACKGROUND
Infection with Helicobacter pylori (H. pylori) leads to the initiation of innate immune responses with increased antimicrobial peptide (AMP) expression in the gastric epithelium. This study aimed to determine the expression of the novel peptides beta-defensin 4 (hBD-4) and RNase 7 in infectious and non-infectious gastritis. Furthermore, pattern recognition receptors and mechanisms of regulation were characterized.


METHODS
Expression of AMPs was quantified by real-time PCR in biopsies obtained from healthy individuals and patients with infectious and non-infectious gastritis as well as in AGS gastric epithelial cells infected with H. pylori. Distribution of hBD-4 in the gastric mucosa was characterized by in-situ hybridisation and immunohistochemistry. The role of Toll-like receptors (TLRs) 2 and 4 and associated signalling pathways was addressed.


RESULTS
hBD-4 was expressed at low levels in gastric epithelial cells and was significantly upregulated in infectious and non-infectious gastritis. Standard eradication but not acid suppression therapy significantly decreased hBD-4 expression. Cytotoxin associated gene (cag)A positive H. pylori significantly increased the expression of hBD-4 whereas cagA negative organisms, non-viable bacteria or culture supernatants had no significant effect. Overexpression and downregulation of TLRs was not associated with an altered hBD-4 expression. However, blocking experiments revealed an essential role for the p38 mitogen-activated protein kinase. RNase7 was inconsistently expressed in biopsies and not significantly upregulated by H. pylori.


CONCLUSIONS
hBD-4 may play a significant role in H. pylori associated gastritis. Inconsistent expression of RNase 7 does not support a pivotal role for this peptide in response to infection with H. pylori.
Otte
J-M
JM
Ruhr-University, Bochum, Germany. jan-michel.otte@rub.de
Neumann
H M
HM
Brand
S
S
Schrader
H
H
Schmidt
W E
WE
Schmitz
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D016022:Case-Control Studies; D054804:Cathelicidins; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology; D015870:Gene Expression; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D055815:Young Adult; D023083:beta-Defensins / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023083:beta-Defensins; D012260:Ribonucleases; C470000:Ribonuclease 7