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. MATERIALS AND 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.

Reaction of phenylaminoethyl selenides with peroxynitrite and hydrogen peroxide.

Peroxynitrite, a reactive cytotoxic species generated by the reaction of superoxide with nitric oxide, rapidly oxidizes phenylaminoethyl selenide (PAESe) and its para-substituted derivatives with second-order rate constants ranging from 900 to 3000 M(-1) s(-1) at neutral pH (pH 7.0) and 25 degrees C. These values are approximately 3 x 10(4) times greater than the corresponding rate constants for the reactions of selenides with hydrogen peroxide. The peroxynitrite reaction was also studied at alkaline pH. HPLC analysis confirms that both the peroxynitrite and hydrogen peroxide reactions produced the corresponding phenylaminoethyl selenoxide (PAESeO) as the sole selenium-containing product, with a stoichiometry of 1 mol of PAESe oxidized per 1 mol of PAESeO formed per 1 mol of oxidant reacted. The influence of para-substituents on the rate constants was investigated using Hammett plots; in both cases the data are consistent with an S(N)2-type mechanism, wherein the selenium atom acts as the nucleophile. Our results provide further evidence that organoselenium compounds may play a protective role in the defense against the many reactive oxidizing species produced in cellular metabolism.