IL-1 Receptor-associated Kinase M Downregulates DSS-induced Colitis
IL-1 Receptor-associated Kinase M Downregulates DSS-induced Colitis
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DOI：
10.1002/ibd.21287
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发表时间：
2010-10-01
影响因子：
4.9
通讯作者：
Hultgren, Olof H.
中科院分区：
文献类型：
--
作者：
Berglund, Martin;Melgar, Silvia;Hultgren, Olof H.
背景：溃疡性结肠炎与结肠通透性增加有关，导致细菌移位进入固有层。我们调查的重要性Toll样受体（TLR）调节蛋白IL-1受体相关激酶M（IRAK-M）使用糜烂性葡聚糖硫酸钠（DSS）诱导的colis.Methods模型：IRAK-M-主管和无能小鼠进行治疗，3% DSS 5天，然后2天的定期饮水。对疾病的临床体征随访7天。第7天，处死小鼠，收集血浆和组织进行组织病理学检查并分析细胞因子和趋化因子的产生以及T细胞转录因子的表达。结果：在第7天，IRAK-M缺陷型小鼠显示总体重降低（77.1 +/- 2.1对比88.5 +/- 2.0，*P=0.002）和肉眼可见的增加（2.7 +/- 0.2对比1.6 +/- 0.1，*P 0.002）和组织病理学（6.0 +/- 0对比3.3 +/- 60.5，*P < 0.001）结肠评分。此外，IRAK-M缺陷小鼠结肠促炎细胞因子mRNA表达增加，血浆中肿瘤坏死因子浓度增加（41.1 +/- 13.5 vs 12.8 +/- 2.0 pg/mL，*P = 0.010）。我们发现IRAK-M在下调DSS结肠炎的诱导和进展中至关重要，从而表明IRAK-M可能是未来介入治疗的靶点。（Inflamm Bowel Dis 2010; 16：1778-1786）
Background: Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced model of colitis.Methods: IRAK-M-competent and -incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T-cell transcription factors.Results: At day 7 IRAK-M-deficient mice display a reduced total body weight (77.1 +/- 2.1 versus 88.5 +/- 2.0, *P=0.002) and an increased macroscopical (2.7 +/- 0.2 versus 1.6 +/- 0.1, *P 0.002) and histopathological (6.0 +/- 0 versus 3.3 +/- 60.5, *P < 0.001) colon score compared to wildtype mice. Furthermore, IRAK-M-deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 +/- 13.5 versus 12.8 +/- 2.0 pg/mL, *P = 0.010) in plasma.Conclusions: This is the first report examining the role of IRAK-M in colitis. We find that IRAK-M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK-M might be a target for future interventional therapies. (Inflamm Bowel Dis 2010; 16: 1778-1786)