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

被引:67
作者
Gijsbers, K
Van Assche, G
Joossens, S
Struyf, S
Proost, P
Rutgeerts, P
Geboes, K
Van Damme, J
机构
[1] Univ Louvain, Rega Inst Med Res, Lab Mol Immunol, Louvain, Belgium
[2] Katholieke Univ Leuven Hosp, Dept Gastroenterol, Louvain, Belgium
[3] Katholieke Univ Leuven Hosp, Dept Pathol, Louvain, Belgium
关键词
interleukin-8; granulocyte chemotactic protein-2; Crohn's disease; inflammatory bowel diseases; angiogenesis;
D O I
10.1002/eji.200324807
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1992 / 2000
页数:9
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