Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease.
Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease.
复制标题
DOI：
10.1136/gutjnl-2012-303252
复制
发表时间：
2014-04
期刊：
影响因子：
24.5
通讯作者：
Kraneveld AD
中科院分区：
文献类型：
--
作者：
Koelink PJ;Overbeek SA;Braber S;Morgan ME;Henricks PA;Abdul Roda M;Verspaget HW;Wolfkamp SC;te Velde AA;Jones CW;Jackson PL;Blalock JE;Sparidans RW;Kruijtzer JA;Garssen J;Folkerts G;Kraneveld AD
脯氨酸-甘氨酸-脯氨酸（PGP）已被证明在几种肺部疾病中通过CXCR 2对中性粒细胞具有趋化作用。PGP是通过基质金属蛋白酶（MMP）8和/或MMP 9和脯氨酰内肽酶（PE）的联合作用从胶原蛋白衍生的。我们研究了PGP在炎症性肠病（IBD）中的作用。在IBD患者和葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠的肠组织中，通过ELISA、免疫印迹和免疫组化检测MMP 8、MMP 9和PE。还相应地分析外周血多形核细胞（PMN）上清液，并与胶原一起孵育以评估离体PGP生成。通过质谱法测量PGP水平，并用PGP拮抗剂和PGP抗体实现PGP中和。在IBD患者的肠道中，MMP 8和MMP 9水平升高，而PE的表达水平与对照组织相似。炎症性肠病患者肠组织中PGP水平升高。在DSS处理的小鼠的肠中获得了类似的结果。来自IBD患者的PMN上清液远比健康对照更能够从胶原离体产生PGP。此外，在DSS诱导的结肠炎期间，PGP中和导致肠中中性粒细胞浸润显著减少。从胶原蛋白产生PGP的蛋白水解级联以及三肽本身存在于IBD患者和DSS诱导的结肠炎小鼠的肠道中。DSS处理的小鼠中的PGP中和显示了PGP引导的肠道嗜中性粒细胞浸润的重要性，并表明IBD中嗜中性粒细胞炎症的恶性循环。
Proline–glycine–proline (PGP) has been shown to have chemotactic effects on neutrophils via CXCR2 in several lung diseases. PGP is derived from collagen by the combined action of matrix metalloproteinase (MMP) 8 and/or MMP9 and prolyl endopeptidase (PE). We investigated the role of PGP in inflammatory bowel disease (IBD). In intestinal tissue from patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis, MMP8, MMP9 and PE were evaluated by ELISA, immunoblot and immunohistochemistry. Peripheral blood polymorphonuclear cell (PMN) supernatants were also analysed accordingly and incubated with collagen to assess PGP generation ex vivo. PGP levels were measured by mass spectrometry, and PGP neutralisation was achieved with a PGP antagonist and PGP antibodies. In the intestine of patients with IBD, MMP8 and MMP9 levels were elevated, while PE was expressed at similar levels to control tissue. PGP levels were increased in intestinal tissue of patients with IBD. Similar results were obtained in intestine from DSS-treated mice. PMN supernatants from patients with IBD were far more capable of generating PGP from collagen ex vivo than healthy controls. Furthermore, PGP neutralisation during DSS-induced colitis led to a significant reduction in neutrophil infiltration in the intestine. The proteolytic cascade that generates PGP from collagen, as well as the tripeptide itself, is present in the intestine of patients with IBD and mice with DSS-induced colitis. PGP neutralisation in DSS-treated mice showed the importance of PGP-guided neutrophilic infiltration in the intestine and indicates a vicious circle in neutrophilic inflammation in IBD.
登录
查看更多内容
影响因子：
6.7
作者：
Naito, Y;Takagi, T;Yoshikawa, T
通讯作者：
Yoshikawa, T
DOI：
10.1164/rccm.200712-1894oc
发表时间：
2008-10-15
影响因子：
24.7
作者：
Rowe, Steven M.;Jackson, Patricia L.;Blalock, J. Edwin
通讯作者：
Blalock, J. Edwin
影响因子：
4.7
作者：
Koelink, Pim J.;Robanus-Maandag, Els C.;Verspaget, Hein W.
通讯作者：
Verspaget, Hein W.
影响因子：
29.4
作者：
GRAHAM, MF;DIEGELMANN, RF;GAY, R
通讯作者：
GAY, R
影响因子：
4.4
作者：
Gaggar, Amit;Jackson, Patricia L.;Blalock, J. Edwin
通讯作者：
Blalock, J. Edwin