Altered levels of STAT1 and STAT3 influence the neuronal response to interferon gamma

As immune responses in the CNS are highly regulated, cell-specific differences in IFN-gamma signaling may be integral in dictating the outcome of host cell responses. In comparing the response of IFN-gamma-treated primary neurons to control MEF, we observed that neurons demonstrated lower basal expression of both STAT I and STAT3, the primary signal transducers responsible for IFN-gamma signaling. Following IFN-gamma treatment of these cell populations, we noted muted and delayed STAT1 phosphorylation, no detectable STAT3 phosphorylation, and a 3-10-fold lower level of representative IFN-gamma-responsive gene transcripts. Moreover, in response to a brief pulse of IFN-gamma, a steady increase in STAT1 phosphorylation and IFN gamma gene expression over 48 It was observed in neurons, as compared to rapid attenuation in MEF These distinct response kinetics in IFN gamma- stimulated neurons may reflect modifications in the IFN-gamma negative feedback loop, which may provide a mechanism for the cell-specific heterogeneity of responses to IFN-gamma. (c) 2007 Elsevier B.V. All rights reserved.