Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization

Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization
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DOI:
10.3748/wjg.v11.i40.6305
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发表时间:
2005-10-28
影响因子:
4.3
通讯作者:
Goto, Hidemi
Goto, Hidemi
中科院分区:
医学2区
文献类型:
--
作者:
Mizuno, Tomokazu;Ando, Takafumi;Goto, Hidemi

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目的:目的:探讨白细胞介素(IL)-17在胃溃疡形成中的作用。在内窥镜检查期间从胃窦和GU部位获得粘液活检样品。在10 μ g/mL植物血凝素-P(PHA)存在下,将样品用于原位刺激48 h,进行组织学检查和幽门螺杆菌(H pylori)培养。ELISA法测定培养上清中IL-17和IL-8蛋白水平。逆转录聚合酶链反应(RT-PCR)检测IL-17 mRNA的表达。使用线性探针试验(LiPA)通过反向杂交评估幽门螺杆菌cagA和vacA状态。结果:36例GU患者和29例NU患者中15例Hp阳性,14例NU患者Hp阴性;来自GU和NU患者的所有51株幽门螺杆菌菌株均为cagA和vacAs 1/m1阳性。幽门螺杆菌阳性患者胃窦粘膜组织中IL-17水平显著高于未感染患者(幽门螺杆菌阳性NU患者:中位数467 pg/mg/protein,范围53 - 2499;幽门螺杆菌阴性NU患者:中位数104 pg/mg/protein,范围16 - 312,P <0.0005)。溃疡部位IL-17水平(中位数1356pg/mg/protein,范围121~13730;胃窦:中位数761pg/mg/protein,范围24~7620,P <0.005)显著高于胃窦远端。幽门螺杆菌阳性GU和NU患者的活检显示IL-17 mRNA在所有样本中表达,而幽门螺杆菌阴性对照组胃窦的活检显示未检测到表达。GU患者各活检部位IL-17和IL-8水平显著相关(溃疡:r = 0.62,P <0.0001;胃窦:r = 0.61,P <0.0001)。rhIL-17和幽门螺杆菌菌株26 695分别刺激IL-8的生产从AGS cells. CONCLUSION:IL-17可能发挥重要作用,在炎症反应幽门螺杆菌定植,并可能最终影响幽门螺杆菌相关疾病的结果,出现在胃炎的背景下。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: To determine the role of interleukin (IL)-17 in gastric ulcerogenesis.METHODS: Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 mu g/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori (H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26 695 or recombinant human (rh) IL-17.RESULTS: All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2 499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P < 0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1 356 pg/mg/protein, range 121-1 3730; antrum: median 761 pg/mg/protein, range 24-7 620, P < 0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62, P < 0.0001; antrum: r = 0.61, P < 0.0001) in GU patients. RhIL-17 and H pylori strain 26 695 each stimulated IL-8 production from AGS cells.CONCLUSION: IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.