Indeed, our results showed that EMMPRIN ex pression was suppressed by curcumin in a dose dependent manner at both protein and mRNA level, suggesting that the down regulation of EMMPRIN by cur cumin is, CB-7598 at least in part, responsible for the reduction of MMP 9 expression in PMA induced macrophages. Curcumin inhibits chronic AMPK activation induced by PMA We further tested Inhibitors,Modulators,Libraries whether AMPK activation was involved in inhibiting MMP 9 and EMMPRIN expression by curcu min. Cells were pretreated with different doses of curcumin for 1 hour and induced with PMA for another 48 hours, then the phosphorylation of AMPK and total AMPK was examined by Western blot. As shown in Figure 2C D, the total AMPK increased slightly in the PMA group and curcumin can attenuates upregulation of total AMPK protein.

PMA induced the sustained activation of AMPK in THP 1 cells. Importantly, curcumin remarkably abol ished AMPK activation in a dose dependent manner. Curcumin Inhibitors,Modulators,Libraries suppresses MAPK and PKC pathways in PMA induced THP 1 cells Previous studies from other groups and our group indicate that PMA promotes Inhibitors,Modulators,Libraries the level of EMMPRIN and Inhibitors,Modulators,Libraries MMP 9 through activating MAPK signaling pathways. PMA also is a strong inducer of protein kinase C, pkc sig nal paly a role during PMA induced cell differentiation and adhension. Thus, we wondered whether the reduced EMMPRIN expression was through the MAPK or PKC pathway. To test this hypothesis, THP 1 cells were first pre treated with curcumin for 1 hour before incubating with PMA for another 48 hours. Western data showed that cur cumin significantly inhibited the phosphorylation of ERK1 2, p38 MAPK, JNK and PKC, PKCB1 induced by PMA.

To further explore which MAPK signaling involved in the upregulation of MMP 9, MMP13 and EMMPRIN in PMA Inhibitors,Modulators,Libraries induces THP 1 cell. We next examine the expression of them after treated with ERK1 2 specific inhibitor, p38 specific inhibitor, and JNK specific inhibitor. As shown in Figure 4, ERK1 2 and JNK specific inhibitor significantly downregu lated MMP apply for it 9 expression, and activation,and p38 specific in hibitor showed weaker function. ERK1 2 and p38 specific inhibitor inhibitor significantly decreased EMMPRIN expres sion, whereas JNK specific inhibitor showed no inhibitory effect. For MMP 13, ERK1 2, p38 and JNK specific inhibitor at high dose showed remarkable inhibitory effect. In conclusion, our result suggest that MAPK signaling and PKC pathways are involved in the regulation of EMMPRIN, MMP 9 and MMP 13 expression.