Inhibition of lipopolysaccharide-induced in vitro desensitization by interferon-gamma.
Exposure of Mono-Mac-6 cells to lipopolysaccharide (LPS) can induce rapid and transient expression of cytokines like tumor necrosis factor (TNF), interleukin 1 and interleukin 6. Preculture of Mono-Mac-6 cells in culture medium containing small amounts (1-50 ng/ml) of LPS for 3 days leads to an unresponsiveness to a subsequent stimulation with a high amount of LPS. This in vitro desensitization of a monocytic cell line may serve as a model for desensitization to LPS seen in vivo, for example in mice or man repetitively treated with LPS. Addition of interferon-gamma (IFN-gamma) to the Mono-Mac-6 cells during the LPS preculture period leads to an inhibition of desensitization, whereas addition of IFN-alpha or IFN-beta is not able to inhibit the LPS-induced desensitization. The inhibition of desensitization by IFN-gamma was dose dependent and time dependent. Preculture of Mono-Mac-6 cells with LPS leads to a strong reduction of TNF mRNA. This reduction of specific mRNA is also overcome by addition of IFN-gamma, but not by IFN-alpha and IFN-beta, indicating that pretranslational mechanisms are responsible for the regulation of TNF in desensitization.
Haas
J G
JG
Institute for Immunology, University of Munich, FRG.
Meyer
N
N
Riethmüller
G
G
Ziegler-Heitbrock
H W
HW
D002460:Cell Line; D015536:Down-Regulation; D004361:Drug Tolerance; D006801:Humans; D007370:Interferon Type I / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007370:Interferon Type I; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma