Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli

被引:112
作者
Hedlund, M [1 ]
Svensson, M [1 ]
Nilson, A [1 ]
Duan, RD [1 ]
Svanborg, C [1 ]
机构
[1] LUND UNIV, DEPT MED, DIV GASTROENTEROL, S-22362 LUND, SWEDEN
关键词
D O I
10.1084/jem.183.3.1037
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Escherichia coli express funbriae-associated adhesins through which they attach to mucosal cells and activate a cytokine response. The receptors for E. coli P finbriae are the globoseries of glycosphingolipids; Gal alpha 1-->4Gal beta-containing oligosaccharides bound to ceramide in the outer leaflet of the lipid bilayer. The receptors for type 1 fimbriae are mannosylated glycoproteins rather than glycolipids. This study tested the hypothesis that P-fimbriated E. coli elicit a cytokine response through the release of ceramide in the receptor-bearing cell. We used the A498 human kidney cell line, which expressed functional receptors for P and type 1 fimbriae and secreted higher levels of interleukin (IL)-6 when exposed to the fimbriated strains than to isogenic nonf;mbriated controls. P-fimbriated E. coli caused the release of ceramide and increased the phosphorylation of ceramide to ceramide 1-phosphate. The IL-6 response to P-fimbriated E. coli was reduced by inhibitors of serine/threonine kinases but not by other protein kinase inhibitors. In contrast, ceramide levels were not influenced by type 1-fimbriated E. coli, and the IL-6 response was insensitive to the serine/threonine kinase inhibitors. These results demonstrate that the ceramide-signaling pathway is activated by P-fimbriated E. coli, and that the receptor specificity of the P fimbriae influences this process. We propose that this activation pathway contributes to the cytokine induction by P-fimbriated E. coli in epithelial cells.
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页码:1037 / 1044
页数:8
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