CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue
CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue
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DOI：
10.1002/eji.200324807
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发表时间：
2004-07-01
影响因子：
5.4
通讯作者：
Van Damme, J
中科院分区：
文献类型：
--
作者：
Gijsbers, K;Van Assche, G;Van Damme, J
克罗恩病 (CD) 和溃疡性结肠炎 (UC) 是炎症性肠病 (IBD)，其特征是慢性肠道炎症和促炎细胞因子和趋化因子介导的白细胞持续涌入。评估了CXCR1结合趋化因子IL-8/CXCL8和GCP-2/CXCL6的肠道表达以及免疫活性细胞在IBD中的参与。 IBD 患者的外周血单核细胞 (PBMC) 经内毒素、植物凝集素或双链 RNA 刺激后产生的 IL-8 在 CID 患者中显着降低，但在 UC 患者或健康受试者中没有显着降低。 IBD 患者的 PBMC 趋化因子产生减少是 IL-8 和 CID 特异性的，但不依赖于诱导剂。在血清中，大多数趋化因子仍然检测不到，而 IBD 患者中可测量的趋化因子水平保持不变。 IBD 患者发炎肠道组织中的内皮细胞高表达 GCP-2，而非 ENA-78/CXCL5 和 IL-8。相反，受刺激的内皮细胞培养物产生的 IL-8 多于 GCP-2。溃疡部位内皮细胞的选择性 GCP-2 染色表明，尽管 GCP-2 在体外的生产能力较低，但它在 IBD 中的作用不同于结构上 (ENA-78) 和功能上 (IL-8) 相关的 ELR+ CXC 趋化因子。因此，趋化因子网络显示出互补性而不是冗余性。
Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that are characterized by chronic intestinal inflammation and a constant influx of leukocytes mediated by pro-inflammatory cytokines and chemokines. The intestinal expression of the CXCR1-binding chemokines IL-8/CXCL8 and GCP-2/CXCL6 and the participation of immunocompetent cells in IBD were evaluated. IL-8 production by peripheral blood mononuclear cells (PBMC) from IBD patients, stimulated with endotoxin, plant lectin or double-stranded RNA, was significantly lowered in patients with CID, but not in UC patients or healthy subjects. The reduced chemokine production by PBMC from IBD patients was both IL-8 and CID specific, but not inducer dependent. In serum, most chemokines remained undetectable, while the levels of those that were measurable remained unaltered in IBD patients. GCP-2, but not ENA-78/CXCL5, nor IL-8, were highly expressed by endothelial cells in inflamed intestinal tissue of IBD patients. In contrast, stimulated endothelial cell cultures produced more IL-8 than GCP-2. The selective GCP-2 staining of endothelial cells at sites of ulcerations suggests that GCP-2, despite its low production capacity in vitro, plays a role in IBD that is different from that of structurally (ENA-78) and functionally (IL-8) related ELR+ CXC chemokines. Thus, the chemokine network shows complementarity rather than redundancy.