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

It has been shown that interferon-γ (IFN-γ) plays a role in the regulation of interleukin-8 (IL-8), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) secretion by macrophages stimulated with lignin derivatives, such as EP3, and lipopolysaccharides (LPS) [Cytokine 11 (1999) 571]. To examine the mechanism by which IFN-γ affects secretion of these factors, EP3- or LPS-stimulated macrophages were treated with different concentrations of IFN-γ, and mRNA levels of IL-8, nitric oxide synthase (NOS) and TNF-α 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-α mRNAs. IFN-γ 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-γ appeared to increase the level of NOS mRNA both in unstimulated and stimulated macrophages. IFN-γ, which increased the amount of TNF-α mRNA in unstimulated macrophages, showed no significant effect on the high level of TNF-α mRNA in stimulated macrophages. These results suggest that IFN-γ 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-γ on TNF-α secretion by stimulated macrophages may be mediated by a different mechanism.