Modulation of host antimicrobial peptide (β-defensins 1 and 2) expression during gastritis
Modulation of host antimicrobial peptide (β-defensins 1 and 2) expression during gastritis
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DOI：
10.1136/gut.51.3.356
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发表时间：
2002-09-01
期刊：
影响因子：
24.5
通讯作者：
Farthing, MJG
中科院分区：
文献类型：
--
作者：
Bajaj-Elliott, M;Fedeli, P;Farthing, MJG
背景：β-防御素是新近发现的一类抗菌肽家族，由粘膜表面上皮细胞表达，感染或炎症使其产生增多。幽门螺杆菌定植于胃上皮细胞，引起持续性胃炎，导致胃窦和胃体炎症，以及消化性溃疡疾病。目的：为探讨β-防御素在胃上皮细胞对感染和炎症的先天免疫反应中的作用，我们研究了幽门螺杆菌和促炎刺激对人β-防御素1和2(hBD1，hBD2)的mRNA表达和调控。方法：采用定量竞争反转录-聚合酶链式反应(RT-PCR)技术，研究不同刺激条件对胃上皮细胞株(AGS、MKN7、MKN45)中hBD1、hBD2表达的影响。采用半定量RT-PCR方法检测胃炎组织中防御素mRNA的表达，并与正常对照组进行比较。结果：细胞毒性幽门螺杆菌和白介素1β均能明显上调AGS和MKN7细胞hBD2的表达，且呈剂量和时间依赖关系。在感染期间，hBD1的表达也略有增加。有趣的是，仅在MKN7细胞中观察到IL-1β诱导hBD1基因表达。与hBD2的表达相比，这种反应的幅度延迟和降低。正常胃窦组织中未检测到hBD2的表达，而幽门螺杆菌阳性胃炎组织中hBD2的表达明显高于对照组(P<0.05)。
Background: beta-Defensins are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces where their production is augmented by infection or inflammation. Helicobacter pylori colonises the gastric epithelium causing persistent gastric inflammation leading to antral and corpus gastritis, and peptic ulcer disease.Aims: To evaluate the role of beta-defensins in the innate immune response of the gastric epithelium to infection and inflammation, we have assessed mRNA expression and regulation of human beta-defensins 1 and 2 (hBD1, hBD2) by H pylori and proinflammatory stimuli. We have also compared gene and peptide expression of these bactericidal agents in H pylori induced gastritis with that in normal gastric mucosa.Methods: Modulation of expression of hBD1 and hBD2 by various stimuli was studied in three (AGS, MKN7, MKN45) gastric epithelial cell lines by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR). Defensin mRNA expression was measured by semiquantitative RT-PCR in gastritis tissue and compared with controls. Peptide localisation was assessed by immunohistochemistry.Results: Cytotoxic H pylori and interleukin 1beta (IL-1beta) markedly upregulated expression of hBD2 in a dose and time dependent manner in both AGS and MKN7 cell lines. A modest increase in hBD1 expression was also noted during infection. Interestingly, induction of hBD1 gene expression by IL-1beta was only observed in MKN7 cells. The magnitude of this response was delayed and reduced compared with hBD2 expression. In gastric biopsies, hBD2 was undetectable in normal gastric antrum but a marked increase was observed in H pylori positive gastritis compared with control tissue (p