Actions of exogenous and endogenous IL-10 on glial responses to bacterial LPS/cytokines.
The objective of this study was to investigate the actions of exogenous and endogenous IL-10 on inflammatory responses of glia. Studies were conducted in primary, mixed glial cultures from C57BL/6 (wild-type [WT]) and IL-10-deficient C57BL/6 (IL-10 knockout [KO]) neonatal mice. Activation of cultures from WT mice by bacterial lipopolysaccharide (LPS, 10 ng/ml-10 microg/ml, 24 h), caused dose-dependent increases in nitric oxide (NO) and prostaglandin E(2) (PGE(2)) release. In cultures from IL-10 KO mice, LPS elicited markedly attenuated release of NO (approximately 4-fold) and PGE(2) (approximately 17-fold). In WT cultures, co-incubation with IL-10 (10 or 100 ng/ml, 24 h) inhibited the effects of LPS on release of NO (30%) and PGE(2) (40-50%). In cultures from IL-10 KO mice, the addition of IL-10 (10 or 100 ng/ml, 24 h) completely abolished LPS-induced NO and PGE(2) release. LPS did, however, release of IL-1beta and TNF-alpha in cultures from all animals. Co-incubation of WT cultures with IL-10 (1, 10, or 100 ng/ml, 24 h) dose-dependently reduced the release of IL-1beta (by 0%, 15%, 75%, respectively). In cultures from IL-10 KO mice, co-incubation with IL-10 (1, 10, or 100 ng/ml, 24 h) completely abolished LPS induced release of IL-1beta. Co-incubation with IL-10 (1, 10, 100 ng/ml) reduced, LPS-induced TNF-alpha release dose-dependently in WT cultures (by 15%, 50% and 90%) and abolished LPS-induced TNF-alpha release in cells from IL-10 KO mice. These results indicate that in glia from WT mice, exogenous IL-10 attenuates LPS-induces release of NO, PGE(2), TNF-alpha and IL-1beta. In contrast, mixed glial cultures from IL-10 KO mice showed reduced responses to LPS, but increased sensitivity to exogenous IL-10.
Molina-Holgado
F
F
School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Grencis
R
R
Rothwell
N J
NJ
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004660:Encephalitis / Q000378:metabolism* / Q000503:physiopathology*; D004731:Endotoxins / Q000378:metabolism; D005434:Flow Cytometry; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015232:Dinoprostone; D009585:Nitrogen Dioxide