selleck bio Glutathione related The genes for several proteins involved in glutathione metabolism and secretion were regulated by the different types of mixtures of cytokines. Subunits of glu tathione S transferase were generally downregulated, while both Th1 and MM upregulated P glycopro tein by 5 fold, p 0. 10 and p 0. 05, respectively. Transcription factors Th1 cytokines markedly upregulated junB, CREB and the p105 subunit of NF ?B. Both Th1 and MM cytokines altered expression of genes for several other transcription factors, while the Th2 cytokines had minimal effects. All three cytokines markedly upregulated mes sage levels of junB and downregu lated hepatic nuclear factor alpha. Both Th1 and MM cytokines upregulated the expression of the gene for NF kappa B p105 subunit and downregu lated the aryl hydrocarbon receptor.

Inhibitors,Modulators,Libraries Lipid synthesis and signaling As noted in Table 2, the genes for several proteins involved in lipid metabolism and signaling were regu lated by the different cytokine mixtures. For example, fatty acid CoA ligase long chain 4 was downregulated 4 to 5 fold by Th1 and Mm cytokines, while UDP glucose ceramide glycosyl Inhibitors,Modulators,Libraries transferase was upregu lated 3 fold. With regard to lipid signaling, CDP diacylglycerol synthase was markedly upregulated 610 fold by all three cytokines, while EDG was downregulated 6 fold by MM cytokines. Steroid and vitamin D related Nuclear receptors Th1 and MM cytokines upregulated the gene for peroxi some proliferator activator receptor ? by 2 fold, and downregulated the gene for PPAR ? by 5 fold. Th2 cytokines downregulated the gene for PPAR ? but had no effect on PPAR ?.

Signaling The cytokine mixtures had effects on the expression of genes for many signal transduction molecules, some of which are presented in Table 2. Among these are STAT1, 3 and 5, JAK2, homer and protein kinase 2 B. Of interest, only one gene in this category was affected by Th2 cytokines, Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries stress activated protein kinase alpha 2, upregu lated 3 fold. Cytoplasmic transport and degradation of proteins Th1, MM and Inhibitors,Modulators,Libraries Th2 cytokines had effects on the genes for several proteins involved in synthesis, degradation and intracellular transport of proteins including synucleins, proteasome subunits, ubiquitin conjugating enzymes and heat shock protein 70 kDa. For example, proteasome alpha 6 was upregulated 10 fold by Th1 cytokines, while the ubiquitin conjugat ing enzyme E2D 2 was downregulated 4 to 6 fold by all three cytokine mixtures. Specific genes regulating proteins involved in sterol and vitamin D metabolism were also regulated by the cytokine mixtures. Thus, 17 beta hydroxyl sterol reduct ase was downregulated 4 selleck chemicals MEK162 to 5 fold by Th1 and Th2 cytokines, and testosterone 6 beta hydroxylase was downregulated 7 fold by MM cytokines.