IL-12, while beneficial, is not essential for the host response to VSV encephalitis.
In this report, the role of STAT4 and local production of interleukin (IL)-12 in the central nervous system (CNS) were examined during experimental vesicular stomatitis virus (VSV) encephalitis. We have previously shown that IL-12 treatment is beneficial both in vitro and in vivo during experimental VSV infection. This inhibition of VSV replication was dependent on the production of nitric oxide (NO) by the neuronal isoform of nitric oxide synthase (NOS-1). In vitro, IL-12 induces the phosphorylation and nuclear localization of STAT4 in neuroblastoma cell lines. STAT4 expression was not required for host survival or clearance of virus during experimental VSV encephalitis. Taken together, these data suggest that while neurons can respond directly to IL-12 in vitro by signaling through STAT4, STAT4 is not required for survival. It is likely that redundant innate host inflammatory cytokine responses compensate for the absence of IL-12 signaling.
Chesler
David A
DA
Deparment of Biology, New York University, 1009 Main Building, 100 Washington Square East, New York, NY 10003, USA.
Reiss
Carol Shoshkes
CS
D000818:Animals; D016466:CHO Cells; D002490:Central Nervous System / Q000821:virology; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018792:Encephalitis, Viral / Q000276:immunology* / Q000821:virology; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000821:virology; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development; D014779:Virus Replication
D004268:DNA-Binding Proteins; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12