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 IFNgamma signaling may be integral in dictating the outcome of host cell responses. In comparing the response of IFNgamma-treated primary neurons to control MEF, we observed that neurons demonstrated lower basal expression of both STAT1 and STAT3, the primary signal transducers responsible for IFNgamma signaling. Following IFNgamma 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 IFNgamma-responsive gene transcripts. Moreover, in response to a brief pulse of IFNgamma, a steady increase in STAT1 phosphorylation and IFNgamma gene expression over 48 h was observed in neurons, as compared to rapid attenuation in MEF. These distinct response kinetics in IFNgamma-stimulated neurons may reflect modifications in the IFNgamma negative feedback loop, which may provide a mechanism for the cell-specific heterogeneity of responses to IFNgamma.
Rose
R Wesley
RW
Department of Biology, Arcadia University, 450 South Easton Road, Glenside, PA 19038, United States.
Vorobyeva
Anna G
AG
Skipworth
Jason D
JD
Nicolas
Emmanuelle
E
Rall
Glenn F
GF
D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma