Suppression of interleukin-6 production in endotoxin tolerance in a mouse glioma cell line: reversal by phorbol ester.
Tolerance to endotoxin (lipopolysaccharide, LPS) was shown to be mediated by an inhibition of cytokine production. We have studied the effect of 3-day pretreatment with LPS on production of IL-6 in response to a subsequent challenge with LPS in a mouse glioma. The results indicated that in this model, a complete blockage of IL-6 production is induced by LPS pretreatment. This is associated with a decrease of LPS-induced IL-6 mRNA levels. LPS-induced IL-6 production can be restored by PMA, as it was previously observed in vivo, suggesting that down-regulation of IL-6 response in LPS tolerance occurs at the transcriptional level, probably by down-regulating protein kinase C or some other PMA-activable signaling system. IL-6 production is also down-regulated by 3-day preincubation with IL-6 and, to a lesser extent, with IL-1 or TNF, indicating that IL-6 can down-regulate its own production.
Sironi
M
M
Mario Negri Institute for Pharmacological Research, Milan, Italy.
Bianchi
M
M
Riganti
F
F
Ghezzi
P
P
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D004351:Drug Resistance; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate