5 h. These ubiquitination and de ubiquiti nation mechanisms are emerging as important regula tors of Toll like receptor signaling. Recent findings on TLR signaling pathways have shown that Ub is a key molecule of the NF B inhibitory proteins http://www.selleckchem.com/products/CP-690550.html that can prevent the formation of signaling complexes. Therefore, interfering with ubiquitination activity may prove to be a useful strategy for developing therapeutics targeting severe inflammatory diseases. We show here that both shikonin and emodin may act as immediate early inhibitors of inflammation through interfering with ubiquitin pathways, their use as anti inflammatory remedy may warrant future evaluation, especially since we have shown that shikonin can be very effective in vivo in wound healing activities in skin tissue.

Although BF S L Ep did not inhibit the early macro phage activation stage at 0. 5 h, high suppression of gene expression was however observed at 12 h, which continued for up to 48 h. TRANSPATH database analysis suggested that the level of ubiquitination of Rad23A regulated by Ub protein ligase may be increased. This indicates that BF S L Ep may not have strong inhibitory activity in the early stage of the immune response and may be more immunomodulatory than immunosuppressive. On the other hand, although very few immune related genes were strongly affected by cytopiloyne and BF S L Ep, the gene expression pattern of these two treatments displayed an obvious similarity. The resemblance between BF S L Ep and cytopiloyne treatments was even more evident in analysis of the time profile of the gene expression ratio compared to LPS stimulation, which was characterized by an up regulation of gene expression after 4 h of stimulation.

Despite the overall similarity, cytopiloyne showed some mechanistic differences contributing to the delayed down regulation of genes at 2 h, which was not seen in the BF S L Ep treatment. To study the detailed mechanism responsible for the similar effects of BF S L Ep and cytopiloyne treatment, we compared the expression profiles of those genes that shared common regulation modes between the two treatments. BF S L Ep and cytopiloyne did not show any significant differences in the up group, whereas there were significant differences in the down group. The same scenario was observed with the genes displaying the early no response followed by up regulation mode.

This analysis further sup ports the idea that both Asteraceae preparations may affect common master regulator to modulate the expression of immune genes, which are up regulated at 4 h, and alleviate the down regulation of genes inhibited by LPS stimulation. We then analyzed these groups of genes using the TRANSPATH database, which identified the ERK1 2 pathway as a common key regulator at no more than 4 hierarchical levels of gene GSK-3 regulation.