Obvi ously this includes a vast number of genes and gene prod ucts involved in transcription, cell signaling, mitochondrial function and apoptosis along with many others. In addition to the changes in genes for proteins associated with apoptosis and mitochondria, in our current and prior studies, we found that Th1 cytokines upreg ulated other genes reported to be regulated in the CNS in selleckchem Abiraterone ischemia including adhesion molecules , cytokines and chemokines and their receptors, death and survival proteins, pro teases and inhibitors and growth factors. Th1 cytokines did not affect the gene for e selectin but upregulated the gene for its ligand. Among other genes for proteins regulated in CNS ischemia, Th1 cytokines down regulated genes for neurotrophins and their receptors, and cytokines, chemokines and their relevant receptors.

MM cytokines upregulated genes for cell adhe sion molecules, HSP 70, cytokines, chemokines and receptors, FGF 5 and 10, and MMPs and inhibitors and downregulated genes Inhibitors,Modulators,Libraries of interest for response to ischemia, including TGF ?3, NT3, and FGF2. Th2 cytokines upregulated ischemia related genes for growth factors, cytokines and chemokines and receptors and down regulated genes for IL 1R type I, and NT3. Differential Inhibitors,Modulators,Libraries expression of many of these genes were reported in the NAWM of some patients with MS. As previously reported, Th1, MM and Th2 cytokines had varying effects on the genes for molecules that are involved in altering in the cells of the blood brain barrier including several adhesion molecules and MMPs although our cultures do not contain endothelial cells.

Some of these molecules are undoubtedly important in glial cells as well. In a previous study, we detected upreg ulation of the gene for VEGF. Inhibitors,Modulators,Libraries Upregulation of VEGF could contribute to endothelial cell proliferation seen in some MS lesions producing local hypoxia and oligoden droglial death. The function of VEGF in glial cells as well as other non glial Inhibitors,Modulators,Libraries non neuronal cells, such as pericytes, which conceivably might be in our cultures is not known. Since inflammatory cytokines were able to upregulate the gene for VEGF as well as other genes that are associated with ischemia and the response to ischemia, our data sug gests that cytokine release secondary to inflammation can lead to changes compatible with hypoxia and perhaps to induction of hypoxia itself. We recognize the limitations of microarray analysis as well as gene expression studies since post transcriptional and post translational changes are not detected. In addi tion proteins such as receptors may be present in suffi cient amount to be ligated and involved in a biologic Inhibitors,Modulators,Libraries process without requiring additional selleck chemical Belinostat protein in the short run and thus no upregulation of gene for that protein.