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.
Netea
M G
MG
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Kullberg
B J
BJ
van der Meer
J W
JW
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