Sphingomyelin, glycosphingolipids and ceramide signalling in cells exposed to P-fimbriated Escherichia coli.
Uropathogenic Escherichia coli attach to epithelial cells through P fimbriae that bind Galalpha1-4Galbeta-oligosaccharide sequences in cell surface glycosphingolipids. The binding of P-fimbriated E. coli to uroepithelial cells causes the release of ceramide, activation of the ceramide signalling pathway and a cytokine response in the epithelial cells. The present study examined the molecular source of ceramide in human kidney A498 cells exposed to P-fimbriated E. coli. Agonists such as TNF-alpha and IL-1beta released ceramide from sphingomyelin by the activation of endogenous sphingomyelinases and hydrolysis of sphingomyelin, and triggered an IL-6 response. P-fimbriated E. coli caused a slight increase in endogenous sphingomyelinase activity, but there was no associated sphingomyelin hydrolysis. Instead, the concentration of galactose-containing glycolipids decreased. We propose that P-fimbriated E. coli differ from other activators of the ceramide pathway, in that release of ceramide is from receptor glycolipids and not from sphingomyelin. Receptor breakdown may be an efficient host defence strategy, as it reduces the concentration of cell surface receptors, releases soluble receptor analogues and activates an inflammatory response.
Department of Laboratory Medicine, Lund University, Sweden. maria.hedlund@mmb.lu.se
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Hedlund
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Duan
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Nilsson
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Svanborg
D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D002794:Choline / Q000032:analysis; D002855:Chromatography, Thin Layer; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D005690:Galactose / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000032:analysis; D010767:Phosphorylcholine / Q000494:pharmacology; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism / Q000494:pharmacology; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019459:Urothelium / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology
D002518:Ceramides; D006028:Glycosphingolipids; D007375:Interleukin-1; D015850:Interleukin-6; D013109:Sphingomyelins; D014409:Tumor Necrosis Factor-alpha; D010767:Phosphorylcholine; D013108:Sphingomyelin Phosphodiesterase; D002794:Choline; D005690:Galactose