Blockade of adenosine A2B receptors ameliorates murine colitis.
Blockade of adenosine A2B receptors ameliorates murine colitis.
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腺苷A2B受体的阻断可改善鼠类结肠炎。
DOI：
10.1038/bjp.2008.227
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发表时间：
2008-09
影响因子：
7.3
通讯作者：
Sitaraman, S. V.
中科院分区：
文献类型：
--
作者：
Kolachala, V. L.;Ruble, B. K.;Vijay-Kumar, M.;Wang, L.;Mwangi, S.;Figler, H. E.;Figler, R. A.;Srinivasan, S.;Gewirtz, A. T.;Linden, J.;Merlin, D.;Sitaraman, S. V.
腺苷2B（A2 B）受体是在结肠中表达的主要腺苷受体。通过A2 B受体起作用，腺苷介导肠上皮细胞中的氯化物分泌以及纤连蛋白和白细胞介素（IL）-6的合成和分泌。A2 B受体mRNA和蛋白质表达在人类和小鼠结肠炎期间增加。然而，A2 B受体在肠道炎症反应活化中的作用尚不清楚。在这项研究中，我们研究了A2 B受体拮抗剂对小鼠结肠炎的影响。使用葡聚糖硫酸钠（DSS）处理的小鼠和吡罗昔康处理的IL-10−/−小鼠作为结肠炎的动物模型。在饲料中给予A2 B受体选择性拮抗剂ATL-801。与单独用DSS处理的小鼠相比，沿着饲喂ATL-801的小鼠显示出显著更低的结肠炎程度和严重性，如通过降低的临床症状、组织学评分、IL-6水平和增殖指数所示。ATL-801给药可防止体重减轻，抑制炎症浸润至结肠粘膜，并减少吡罗昔康治疗的IL-10−/−小鼠的上皮增生。ATL-801给药显著降低了结肠炎小鼠结肠器官培养物上清液中IL-6和角质形成细胞衍生的趋化因子（KC）浓度。总之，这些数据表明，肠上皮A2 B受体是肠道促炎反应的重要介质，并且A2 B受体阻断剂可能是治疗炎性肠病的有效治疗策略。
The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein expression are increased during human and murine colitis. However, the effect of the A2B receptor in the activation of the intestinal inflammatory response is not known. In this study, we examined the effect of A2B receptor antagonism on murine colitis. Dextran sodium sulphate (DSS)-treated mice and piroxicam-treated IL-10−/− mice were used as animal models of colitis. The A2B receptor-selective antagonist, ATL-801, was given in the diet. Mice fed ATL-801 along with DSS showed a significantly lower extent and severity of colitis than mice treated with DSS alone, as shown by reduced clinical symptoms, histological scores, IL-6 levels and proliferation indices. The administration of ATL-801 prevented weight loss, suppressed the inflammatory infiltrate into colonic mucosa and decreased epithelial hyperplasia in piroxicam-treated IL-10−/− mice. IL-6 and keratinocyte-derived chemokine (KC) concentrations in the supernatants of colonic organ cultures from colitic mice were significantly reduced by ATL-801 administration. Taken together, these data demonstrate that the intestinal epithelial A2B receptor is an important mediator of pro-inflammatory responses in the intestine and that A2B receptor blockade may be an effective therapeutic strategy to treat inflammatory bowel disease.
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影响因子：
5
作者：
Mabley, J;Soriano, F;Szabó, C
通讯作者：
Szabó, C
影响因子：
3.1
作者：
Vetuschi, A;Latella, G;Gaudio, E
通讯作者：
Gaudio, E
影响因子：
29.4
作者：
Odashima, M;Bamias, G;Cominelli, F
通讯作者：
Cominelli, F
DOI：
10.1084/jem.20050421
发表时间：
2005-10-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Li C;Dandridge KS;Di A;Marrs KL;Harris EL;Roy K;Jackson JS;Makarova NV;Fujiwara Y;Farrar PL;Nelson DJ;Tigyi GJ;Naren AP
通讯作者：
Naren AP
影响因子：
29.4
作者：
Castaneda, FE;Walia, B;Sitaraman, SV
通讯作者：
Sitaraman, SV