Bromelain, from Pineapple Stems, Proteolytically Blocks Activation of Extracellular Regulated Kinase-2 in T Cells

摘要: Recently, it has emerged that extracellular proteases have specific regulatory roles in modulating immune responses. Proteases may act as signaling molecules to activate the Raf-1/extracellular regulated kinase (ERK)-2 pathway participate mitogenesis, apoptosis, and cytokine production. Most reports on role of protease-mediated cell signaling, however, focus their stimulatory effects. In this study, we show for first time also block signal transduction. We bromelain, a mixture cysteine from pineapple stems, blocks activation ERK-2 Th0 cells stimulated via TCR with anti-CD3epsilon mAb, or combined PMA calcium ionophore. The inhibitory activity bromelain was dependent its proteolytic activity, inhibition abrogated by E-64, selective protease inhibitor. However, effects were not caused nonspecific proteolysis, trypsin had no effect ERK activation. Bromelain inhibited PMA-induced IL-2, IFN-gamma, IL-4 mRNA accumulation, but TCR-induced This data suggests critical requirement production, did directly, p21ras activation, an effector molecule upstream Raf-1/MEK/ERK-2 cascade. results indicate is novel inhibitor T transduction inhibitors intracellular pathways.