We especially focused on genes which have not been previously shown to be curcumin targets. In the first set of experiments, mRNA levels of genes highly up regulated by curcumin compared to con trol cells were assessed. Transcripts of Netrin G1, Platelet endothelial cell adhesion molecule 1, Delta like 1, Plasma cell endoplasmic reticulum protein 1, Peroxisome proliferator www.selleckchem.com/products/carfilzomib-pr-171.html acti vated receptor alpha, and Interleukin 4 were all significantly increased by stimulation with curcumin. Ntng1 showed Inhibitors,Modulators,Libraries the strongest expression differ ence with a change of more than 1800 fold. Perp1 and PPARa transcripts were not significantly expressed in rest ing microglia and were switched on to intermediate levels after curcumin treatment.

All six transcripts after combined LPS curcumin treatment remained simi larly high as after curcumin stimulation alone, Inhibitors,Modulators,Libraries indicating that the effects of curcumin persist in activated microglial cells. In the next series of qRT PCR experiments, down regu lated transcripts known to be involved in pro inflamma tory activation of microglial cells were analyzed. Toll like receptor 2, Early growth response 2, Prosta glandin endoperoxide synthase 2, and Inhibitors,Modulators,Libraries Chemokine ligand 2 showed diminished transcript levels in curcumin treated resting BV 2 cells. In the activated state, microglial cells also had the tendency to expressed lower amounts of these transcript but only Ccl2 levels reached the level of statistical significance. When LPS activated BV 2 cells were incubated in the presence of curcumin, transcription of Interleukin 6, nitric oxide synthase 2, Signal transducer and activator of tran scription 1, and Complement Inhibitors,Modulators,Libraries factor C3 were all repressed.

Inhibitors,Modulators,Libraries Curcumin has an inhibitory effect on microglial migration The induction of several transcripts related to cell motility and adhesion prompted us to study the effect of curcumin on microglial migration. We first cultured BV 2 microglia on plastic dishes until 80% confluence and then created a scratch selleck chemicals Bosutinib with a pipette tip. 12 hours after stimulation of resting microglia or LPS acti vated cells with 20 uM of curcumin, migration into the cell free scratch area was documented. Representative microscopic images clearly showed that curcumin treated resting cells as well as activated BV 2 cells exhibit a highly reduced migratory potential. The statistical analysis of five independent experiments revealed a signifi cantly reduced number of migrating cells when curcumin was present in the culture medium. As an independent measure of microglial cell motility and to study the long term effects of curcumin, we performed transwell migration assays over a period of 24 hours. Simi lar as in the scratch assays, the migratory capacity of BV 2 cells was not changed by the activation agent LPS alone.