Lipopolysaccharide-induced production of tumour necrosis factor and interleukin-1 is differentially regulated at the receptor level: the role of CD14-dependent and CD14-independent pathways.
Cytokine production induced via CD14-dependent and CD14-independent pathways was investigated in mouse peritoneal macrophages incubated with lipopolysaccharide (LPS) or lipid A. Different LPS receptors appear to be responsible for production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) and IL-1 beta. TNF-alpha production is essentially CD14 dependent, both in the presence or absence of plasma. In the presence of plasma, endotoxin-induced IL-1 production is mediated by CD14-dependent mechanisms, while in its absence both CD14-dependent and CD14-independent pathways are involved. Lipid A stimulates cytokine synthesis through both CD14-dependent and CD14-independent mechanisms, but its action is weaker than that of LPS, indicating that the polysaccharide moiety may be necessary for proper stimulation of mouse macrophages by endotoxin.
Department of Medicine, University Hospital Nijmegen, The Netherlands.
M G
MG
Netea
B J
BJ
Kullberg
J W
JW
van der Meer
D000818:Animals; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000096:biosynthesis*; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000494:pharmacology
D007375:Interleukin-1; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C049596:diphosphoryl lipid A; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase