Javamide-II Found in Coffee Is Better than Caffeine at Suppressing TNF-α Production in PMA/PHA-Treated Lymphocytic Jurkat Cells

Recent studies have suggested positive benefits of coffee consumption on inflammation-related diseases, such as liver diseases and diabetes, where activated lymphocytes and TNF-α are critically implicated. Interestingly, some reports suggested that javamide-II found in coffee may have anti-inflammatory activity greater than that of caffeine, but there is limited information about its effect on TNF-α production by activated lymphocytes. Therefore, the inhibitory effect of javamide-II on TNF-α was investigated in PMA/PHA-treated lymphocytic Jurkat cells. At 5 μM, javamide-II, not caffeine, inhibited TNF-α production in the cells (45 ± 4%, P < 0.001). To elucidate the underlying mechanism, the phosphorylation of MAP kinases (ERK, p38, and JNK) was investigated in the Jurkat cells. Javamide-II had little effect on JNK or p38 phosphorylation, but javamide-II (<20 μM) decreased ERK phosphorylation, consequently reducing TNF-α mRNA expression in the cells (P < 0.001). The involvement of ERK phosphorylation was also confirmed by an ERK1/2 inhibitor (SCH772984). Furthermore, javamide-II was also found to inhibit IL-2 production, which is up-regulated by ERK phosphorylation in cells (P < 0.001). These data suggested that javamide-II may be a potent compound to suppress TNF-α production more efficiently than caffeine by inhibiting ERK phosphorylation in Jurkat cells.