Modulation of interleukin-8 and nitric oxide synthase mRNA levels by interferon-gamma in macrophages stimulated with lignin derivatives and lipopolysaccharides.

It has been shown that interferon-gamma (IFN-gamma) plays a role in the regulation of interleukin-8 (IL-8), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-alpha) secretion by macrophages stimulated with lignin derivatives, such as EP3, and lipopolysaccharides (LPS) [Cytokine 11 (1999) 571]. To examine the mechanism by which IFN-gamma affects secretion of these factors, EP3- or LPS-stimulated macrophages were treated with different concentrations of IFN-gamma, and mRNA levels of IL-8, nitric oxide synthase (NOS) and TNF-alpha were determined by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). As reported previously, stimulation of macrophages by EP3 or LPS dramatically induced the expression of IL-8, NOS, and TNF-alpha mRNAs. IFN-gamma clearly decreased the level of IL-8 mRNA in stimulated macrophages, although it did not affect the IL-8 mRNA level in unstimulated macrophages. In contrast, IFN-gamma appeared to increase the level of NOS mRNA both in unstimulated and stimulated macrophages. IFN-gamma, which increased the amount of TNF-alpha mRNA in unstimulated macrophages, showed no significant effect on the high level of TNF-alpha mRNA in stimulated macrophages. These results suggest that IFN-gamma causes changes in IL-8 and NO secretion by stimulated macrophages through its effects on the level of IL-8 and NO mRNA, respectively. Effects of IFN-gamma on TNF-alpha secretion by stimulated macrophages may be mediated by a different mechanism.