Downregulation of tumor necrosis factor expression in the human Mono-Mac-6 cell line by lipopolysaccharide.

Mono-Mac-6 cells, but not U937 cells, can be induced to rapidly express tumor necrosis factor (TNF) mRNA and protein when triggered with lipopolysaccharide (LPS) at 1 microgram/ml. Preincubation of the cells for 3 d with low amounts of LPS (10 ng/ml) results in nearly complete suppression of TNF secretion. This downregulation appears to occur at the pretranslational level since specific mRNA is virtually undetectable under these conditions. By contrast, the same preincubation with 10 ng/ml LPS results in enhanced phagocytosis (28.6-67.2% for Staphylococcus aureus), demonstrating that not all monocyte functions are suppressed. While these results show that only stringent exclusion of LPS from culture media allows for induction of TNF in the Mono-Mac-6 cell line, the pronounced effect of LPS preincubation may also provide a suitable model with which to study the mechanisms of LPS-induced desensitization.