Involvement of interleukin-1 in glial responses to lipopolysaccharide: endogenous versus exogenous interleukin-1 actions.
Interleukin-1beta (IL-1beta) participates in neuroinflammation and neurodegeneration. Its mechanisms of action are not fully understood, but appear to involve complex interactions between neurons and glia. The objective of this study was to determine the involvement of endogenous IL-1beta in inflammatory responses to LPS in cultured mouse glial cells, and compare this to the effects of exogenous IL-1beta. Activation of primary mixed glial cultures by incubation with LPS (1 microgram/ml, 24 h), caused marked (approximately ten-fold) increases in release of NO, twenty-fold increases in PGE(2) and ninety-fold increases of IL-6 release. Incubation with human recombinant IL-1beta (100 ng/ml) also stimulated NO and IL-6 release to a similar extent to LPS, but IL-1beta (1 or 100 ng/ml) caused only modest increases (approximately seven-fold) in PGE(2) release. Co-incubation with IL-1ra inhibited the effects of LPS on NO release (-65%) and IL-6 production (-30%), but failed to reduce PGE(2) release. These results indicate that exogenous IL-1beta induces release of NO, PGE(2) and IL-6 in mixed glial cultures, and that endogenous IL-1beta mediates inflammatory actions of LPS on NO and to a lesser extent IL-6, but not on PGE(2) release in mixed glial cultures. Indeed endogenous IL-1beta appears to inhibit LPS-induced PGE(2) release.
Molina-Holgado
F
F
School of Biological Sciences 1.124 Stopford Building, The University of Manchester, Oxford Road, M13 9PT, Manchester, UK.
Toulmond
S
S
Rothwell
N J
NJ
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; D009569:Nitric Oxide; D015232:Dinoprostone