Protease‐Activated Receptor‐2 (PAR2) in Human Gastric Mucosa as Mediator of Proinflammatory Effects in Helicobacter pylori Infection
Protease‐Activated Receptor‐2 (PAR2) in Human Gastric Mucosa as Mediator of Proinflammatory Effects in Helicobacter pylori Infection
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人胃粘膜中的蛋白酶激活受体 2 (PAR2) 作为幽门螺杆菌感染促炎作用的介质
DOI：
10.1111/j.1523-5378.2011.00866.x
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发表时间：
2011
期刊：
影响因子：
4.4
通讯作者：
Malfertheiner P
中科院分区：
文献类型：
--
作者：
Kandulski A;Kuester;Mönkemüller K;Fry LC;Malfertheiner P
简介：蛋白酶激活受体（PAR）是在整个胃肠道中表达的七种跨膜受体。利用胃癌细胞系、小鼠模型和一项临床研究进行的体外实验为PAR 2在幽门螺杆菌诱导的胃炎中的潜在作用提供了证据。目的：研究PAR 2在幽门螺杆菌感染患者中的表达及其与促炎性IL-8、IL-1β以及粘膜组织学变化的相关性。此外，PAR 2表达与黏膜分泌性白细胞蛋白酶抑制剂（SLPI）（PAR 2的一种假定调节剂）量相关。方法：22例幽门螺杆菌感染患者和72例幽门螺杆菌阴性受试者接受上消化道内镜检查。在胃窦粘膜活检中，通过定量RT-PCR分析PAR 2、IL-1β、IL-8和SLPI表达，部分通过ELISA和免疫组织化学分析。根据更新的悉尼分类法对胃炎进行组织学评价。结果：与未感染幽门螺杆菌的患者相比，幽门螺杆菌感染患者的粘膜中IL-8基因表达增加了5倍（p<.0001），而两组之间未观察到PAR 2和IL-1β mRNA量的差异。 PAR 2基因表达与IL-8、IL-1β的转录水平以及幽门螺杆菌感染患者粘膜SLPI水平呈正相关（r：0.47-0.84;p<0.0001），而与胃炎程度无相关性。结论：PAR 2代表了IL-8分泌和促炎作用在幽门螺杆菌诱导的胃炎中的附加途径。 SLPI水平降低导致感染受试者粘膜中丝氨酸蛋白酶活性升高，可能调节PAR 2活化。
Introduction:Protease‐activated receptors (PAR) are seven transmembrane receptors that are expressed throughout the gastrointestinal tract. In vitro experiments using gastric tumor cell lines, murine models and one clinical study provided evidence for a potential role of PAR2 inHelicobacter pylori‐induced gastritis.Aim:To investigate PAR2 expression inH. pylori‐infected patients and correlation with proinflammatory IL‐8, IL‐1β as well as histologic changes of the mucosa. Furthermore, PAR2 expression was studied in context to mucosal amounts of secretory leukocyte protease inhibitor (SLPI), a putative regulator of PAR2.Methods:Twenty‐twoH. pylori‐infected patients and 72H. pylori‐negative subjects underwent upper GI endoscopy. In antrum‐derived mucosal biopsies, PAR2, IL‐1β, IL‐8, and SLPI expression was analyzed by quantitative RT‐PCR, and in part by ELISA and immunohistochemistry. Histopathologic evaluation of gastritis was performed according to the updated Sydney classification. Results: IL‐8 gene expression was 5‐fold increased in the mucosa ofH. pylori‐infected patients compared with non‐infected (p< .0001), whereas no differences for PAR2 and IL‐1β mRNA amounts were observed between both groups. PAR2 gene expression correlated positively with transcript levels of IL‐8, IL‐1β as well mucosal SLPI levels inH. pylori‐infected patients (r: 0.47–0.84;p< .0001), whereas no correlation was found with the degree of gastritis.Conclusions:PAR2 represents an additive pathway of IL‐8 secretion and proinflammatory effects inH. pylori‐induced gastritis. Reduced SLPI levels leading to higher serine protease activities in the mucosa of infected subjects might regulate PAR2 activation.
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DOI：
10.1097/meg.0b013e3283052ddb
发表时间：
2008-12-01
影响因子：
2.1
作者：
Hosaka, Yoshio;Koslowski, Maureen;Wehkamp, Jan
通讯作者：
Wehkamp, Jan
DOI：
10.25011/cim.v33i2.12352
发表时间：
2010-04
期刊：
Clinical and investigative medicine. Medecine clinique et experimentale
影响因子：
--
作者：
M. Hollenberg
通讯作者：
M. Hollenberg
影响因子：
6
作者：
Cenac, N;Coelho, AM;Vergnolle, N
通讯作者：
Vergnolle, N
影响因子：
1.9
作者：
Inci, Kamuran;Edebo, Anders;Casselbrant, Anna
通讯作者：
Casselbrant, Anna
影响因子：
29.4
作者：
J. Wee;Y. Chionh;Garrett Z Ng;Stacey N. Harbour;C. Allison;C. Pagel;E. Mackie;H. Mitchell;R. Ferrero;P. Sutton
通讯作者：
J. Wee;Y. Chionh;Garrett Z Ng;Stacey N. Harbour;C. Allison;C. Pagel;E. Mackie;H. Mitchell;R. Ferrero;P. Sutton