In agreement with this study, our studies show that although microglia respond to CNTF, the complex formed by CNTF and sCNTFR effectively selleck chemicals promotes Cox 2, PGE2 and CD40 production in microglia whereas CNTF alone is with little effect. Interestingly, the effect of CNTF and sCNTFR was more pronounced in the dendritic like microglia than in Inhibitors,Modulators,Libraries the microglial cultures, which suggests that dendritic like microglia respond more strongly to CNTF sCNTFR. Whereas, exogenous CNTF administra tion has been shown to exert protective effects in MS and EAE, our data and those of others would caution against the use of CNTF as a neuroprotective agent in that the inflammatory side effects subsequent to delivery may limit the clinical usefulness of administering CNTF in treating neurodegenerative diseases, especially where there is an inflammatory component.

Our data Inhibitors,Modulators,Libraries show that CNTF does not activate STAT3 and ERK pathways in microglia. In contrast, Krady et al. showed that rrCNTF elicits a modest increase in STAT3 phosphorylation in rat microglia. Initially we sur mised that the difference in responsiveness was species related, however, subsequent to careful analyses the dis crepancy between those data Inhibitors,Modulators,Libraries and the data reported herein can be attributed to differences in the purity of the micro glial cultures. Rat microglial cultures are typically enriched by incubating non adherent cells obtained from mixed glial cultures on bacteriological dishes. Incubating rat A and C show representative histograms for CD40 expres sion while Panel B and D show representative histograms for MHC Inhibitors,Modulators,Libraries class II expression.

E, Mean fluorescence of CD40, inset shows data from three independent experiments, IFN, IFN plus the combination of CNTF and sCNTFR. F, Mean fluorescence of MHC class II, G, Percentage Inhibitors,Modulators,Libraries of CD40 posi tive cells and inset shows data from three independent experiments. H, Percentage MG132 msds of MHC class II positive cells. Values represent the means S. E. M. from triplicates in one experiment. Different superscript letters indicate significant differences at the p 0. 05 levels as analyzed by one way ANOVA followed by Tukeys post hoc test. Data are repre sentative of 3 independent experiments. microglia on bacteriological dishes for 10 minutes instead of 40 minutes increases the purity of the microglial cultures from 90% to 99% as determined by CD11b and A2B5 staining. In these highly enriched rat microglial cultures STAT3 is not phos phorylated following CNTF treatment whereas in the less enriched microglial cultures CNTF induces STAT3 phos phorylation. This STAT3 signaling likely results from acti vation with the contaminating oligodendrocyte progenitors and, to a smaller degree, astrocytes.