regulator by wes tern blot analysis experiments that showed a delay AZD2281 in inactivation of ERK1 2 activities in THP 1 cells when they were treated with BF S L Ep or cytopiloyne. ERK1 2 activation has long been recognized as a pivotal regulation in macrophage activation and cytokine expres sion during inflammatory responses. ERK1 2 mole cules are phosphorylated on the threonine and tyrosine residues within minutes of TLR 4 stimulation of macro phages and dendritic cells, as shown via treatment with LPS. Our data showing retarded dephosphorylation of ERK1 2 between 2 and 4 h may help to explain the up regulation of several groups of gene expression at 4 h when test cells were treated with BF S L Ep or cytopiloyne. Recent studies have shown that inactivation of MAPK occurs primarily through regulation via depho sphorylation.

The mitogen activated protein kinase phos phatase family includes serine threonine phosphatases, protein tyrosine phosphatases, and members of the dual specificity phosphatases family. There is considerable evidence from both ani mal model and human studies that pharmacological inhi bition of ERK activation may help modify inflammatory responses for clinical applications. Since our data sug gest that cytopiloyne and BF S L Ep can effectively inter fere with the dephosphorylation status of ERK1 2, the DUSPs may thus represent one of the most likely candi dates for such activity. This study and our previous reports have shown that some Asteraceae plant preparations have very desirable pharmacological properties, including low cell toxicity, anti inflammatory bio activity, and a high specific index.

Therefore, the current finding on the mechanistic explanation of the Asteraceae preparations action on ERK regulation warrants further investigation. Interestingly, cytopiloyne also possesses the unique abil ity to delay the suppression of genes downstream of the Lck pathway. The LPS induced NF B path way depends Brefeldin_A on phosphorylation of I B b, and Src tyro sine kinases such as cSrc and Lck, which are key components of the LPS signaling pathway. This suggests that cytopiloyne might affect NF B activation through interference with Lck. Conclusions We used a functional genomics approach to characterize and compare the mechanisms and kinetics of immune modulation of LPS stimulated THP 1 cells by a range of anti inflammatory phytocompounds, including shikonin, emodin, Echinacea extract and cytopiloyne.

Shikonin and emodin exhibit immediate early inhibitory activities, apparently by http://www.selleckchem.com/products/dorsomorphin-2hcl.html interfering with the ubiquitin pathway. Comparative analysis further showed that BF S L Ep and cytopiloyne shared a similar mode of modulation of immune related gene expression during acute inflamma tion, and mode clustering analysis suggested that the ERK1 2 activation pathway was the target of both cyto piloyne and BF S L Ep. These findings may suggest the presence of active compound related to cytopiloyne in Echinacea purpurea preparations, and offer mechanistic insi