Inhibition of tumor necrosis factor-alpha mRNA expression by a limited series of tetrahydroisoquinolines in mouse peritoneal macrophages

ABSTRACT

Tumor necrosis factor-alpha (TNF-alpha) plays important roles in inflammatory responses. Some of tetrahydroisoquinoline (THI) compounds exhibited to inhibit iNOS expression in animal studies and RAW 264.7 cells, but the action of THI on inflammatory reaction was not fully investigated. In the present study, we examined a limited series of THIs (higenamine, YS-51 and THI-52) on the TNF-alpha mRNA expression in mouse peritoneal macrophages by Northern analysis. When thioglycollate-stimulated peritoneal macrophages were incubated with LPS (100 ng/ml), expression of TNF-alpha mRNA was evident and reached its maximum at 2.5 h, which was reduced concentration-dependently by treatment with THIs. When the TNF-alpha activity of macrophage-conditioned media was measured using a TNF-sensitive L929 fibroblast cell line, CCL 1, all THIs increased the cell viability in a concentration dependent manner. The concentrations of THIs used are not cytotoxic by itself when analysed by MTT. Furthermore, nitrite/nitrate level was significantly reduced by the presence of THIs in cells treated with LPS+ interferon-gamma (IFN-gamma). It is concluded, thus, that these results strongly indicated that THIs can suppress the TNF-alpha expression and reduce NO, which may be useful for the inflammatory disorders.