Regulatory mechanisms of murantes and crg-2 chemokine gene induction in central nervous system glial cells by virus

Stephen N. Fisher, Padmavathy Vanguri, Hyun S. Shin, Moon L. Shin

Research output: Contribution to journalArticlepeer-review

Abstract

In this report we characterize the induction mechanisms of two chemokine genes, MuRantes and crg-2, the murine homologs of human RANTES and IP-10, respectively, in primary rat astrocytes and microglia by the neurotropic paramyxovirus, Newcastle Disease Virus (NDV). The time course for NDV induction of both MuRantes and crg-2 genes in astrocytes and microglia was similar, with peak mRNA expression at 10-12 h. Unlike crg-2, MuRantes mRNA was not induced by IFN-γ. MuRantes and crg-2 are transcriptionally induced by noninfectious, UV-irradiated NDV in astrocytes and microglia, unlike TNFα gene transcription, which is induced only by live NDV. These data indicate that signals generated through virus-receptor interaction on the target cell surface suffice to initiate MuRantes and crg-2 gene transcription in the absence of viral replication. In astrocytes, MuRantes mRNA accumulation in response to NDV was completely blocked by tyrosine kinase inhibitors, and partially by PKC and PKA inhibitors, whereas crg-2 mRNA accumulation was significantly inhibited by PKC inhibitors, but minimally or not affected by inhibitors of tyrosine kinase or PKA activity. These kinase inhibitors also affected MuRantes and crg-2 gene transcription in similar patterns to those observed for mRNA levels, but did not reduce the mRNA stability. Therefore, the signals required for mRNA accumulation appear to operate at the level of transcription. Efficient transcription of MuRantes and crg-2 genes may require different sets of transcriptional proteins and enhancers that are regulated by different signaling pathways activated by NDV.

Original languageEnglish (US)
Pages (from-to)331-344
Number of pages14
JournalBrain, Behavior, and Immunity
Volume9
Issue number4
DOIs
StatePublished - Dec 1995

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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