As noted, this is a series of screening experiments and therefore Tables 1 and 2 were prepared using the criteria of 2 fold or 2 fold with a p value of 0. 2 for one or two repli cates of the gene transcript. Unknown genes are not presented. Neurotransmitters and receptors All three cytokine mixtures had regulatory effects on mes sage levels for a wide range inhibitor Y-27632 of message levels for neuro transmitters and their receptors as well as on transporters involved with transmitters including glutamate, adrener gic, cholinergic, glycine, serotonergic, dopaminergic and purinergic systems. The only adrenergic receptor affected was alpha 2 c 4, upregulated 2. 5 fold by Th1 cytokines. Among cholinergic receptors, the largest change Inhibitors,Modulators,Libraries was for nicotinic cholinergic receptor alpha5, downregulated 2. 3 fold by Th1.

Dopaminergic receptors A3 and D1 were markedly downregulated 8 to 14 fold by Th1 and Th2 cytokines. Among several changes in glutamate receptors, Th1 upregulated Inhibitors,Modulators,Libraries ionotropic gluta mate receptor delta 1 by 2. 7 fold, but markedly downregulated metabotropic glutamate receptor 7b by 9. 5 fold. Neuropeptide Y receptor 5 was down regulated by both Th1 and MM cytokine, 18 fold and 8 fold, respectively, while the sub stance P precursor preprotachykinin A was downregulated 7 fold by Th2. For purinergic receptors, the most robust changes were 3 fold downregula tion of P2X1by Th2, and upregulation of P2Y2 by MM and Th2, 3. 5 fold and Inhibitors,Modulators,Libraries 2. 4 fold, respectively, both p 0. 05.

Ion channels Th1, MM and Th2 cytokines had primarily downregula tory effects on expression of a very Inhibitors,Modulators,Libraries large number of genes for proteins that are components of ion channels includ ing Na, K, Ca and Cl channels, both voltage gated and non voltage gated. For example, Th1 and Th2 downregulated the voltage gated alpha 1D L type Ca channel by 4 Inhibitors,Modulators,Libraries and 7 fold respectively, both p 0. 05. A large number of K channels were downregulated by Th2 cytokines, with fewer downregulated by Th1 or MM cytokines. The voltage gated 1 alpha sodium channel was robustly downregulated by Th1 and MM cytokines, 9 fold and 7 fold respectively, while Th2 cytokines uniquely downregulated the 1 beta isoform, 2. 5 fold, p 0. 01. ATPase ion exchangers In addition to the effects on ion channels shown in Table 1, there were effects on Nilotinib supplier several ATPase ion exchangers. With the exception of upregulation of CaATPase by MM cytokines, several ATPase ion exchangers were downregulated by each of the cytokine mixtures. Apoptosis The cytokine mixtures induced up and down regulation of several genes for proteins involved in control of apoptosis including caspase 2, downregulated 3 fold, p 0. 05 by both MM and Th2 cytokines, and caspase 7, downregulated 3 fold by Th1 and MM cytokines.