Otte J-M, Neumann H M, Brand S, Schrader H, Schmidt W E, Schmitz F
Ruhr-University, Bochum, Germany.
Eur J Clin Invest. 2009 Feb;39(2):126-38. doi: 10.1111/j.1365-2362.2008.02071.x.
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.
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.
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.
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.
幽门螺杆菌（H. pylori）感染会引发先天性免疫反应，导致胃上皮细胞中抗菌肽（AMP）表达增加。本研究旨在确定新型肽β-防御素4（hBD-4）和核糖核酸酶7在感染性和非感染性胃炎中的表达情况。此外，还对模式识别受体及其调控机制进行了表征。
通过实时PCR对从健康个体、感染性和非感染性胃炎患者获取的活检组织以及感染幽门螺杆菌的AGS胃上皮细胞中AMP的表达进行定量分析。通过原位杂交和免疫组织化学对hBD-4在胃黏膜中的分布进行表征。探讨了Toll样受体（TLR）2和4及其相关信号通路的作用。
hBD-4在胃上皮细胞中低水平表达，在感染性和非感染性胃炎中显著上调。标准根除治疗而非抑酸治疗可显著降低hBD-4表达。细胞毒素相关基因（cag）A阳性的幽门螺杆菌可显著增加hBD-4的表达，而cagA阴性菌株、无活力细菌或培养上清液则无显著影响。TLR的过表达和下调与hBD-4表达的改变无关。然而，阻断实验揭示了p38丝裂原活化蛋白激酶的重要作用。核糖核酸酶7在活检组织中的表达不一致，且未被幽门螺杆菌显著上调。
hBD-4可能在幽门螺杆菌相关性胃炎中发挥重要作用。核糖核酸酶7的表达不一致不支持该肽在应对幽门螺杆菌感染时起关键作用。
