Ovine IFN-tau modulates the expression of MHC antigens on murine cerebrovascular endothelial cells and inhibits replication of Theiler's virus.
Interferon-beta (IFN-beta) has been used successfully to treat patients with relapsing-remitting multiple sclerosis (MS). IFN-tau is a new class of type I IFN that is secreted by the trophoblast and is the signal for maternal recognition of pregnancy in sheep. IFN-tau has potent immunosuppressive and antiviral activities similar to other type I IFN but is less cytotoxic than IFN-alpha/beta. The current investigation concerns the effect of recombinant ovine IFN-tau (rOvIFN-tau) on the modulation of MHC class I and II expression on cloned mouse cerebrovascular endothelial (CVE) cells. IFN-tau induced tyrosine phosphorylation of Stat1 and upregulated the expression of MHC class I on CVE. One proposed action by which type I IFN reduce the relapse rate in MS is via interference with IFN-gamma-induced MHC class II expression. IFN-tau was shown to downregulate IFN-gamma-induced MHC class II expression on CVE and, hence, may be of potential therapeutic value in downregulating inflammation in the central nervous system (CNS). IFN-tau did not upregulate the expression of MHC class II on CVE. IFN-tau also inhibited the replication of Theiler's virus in CVE. These in vitro results suggest that IFN-tau may be of therapeutic value in the treatment of virus-induced demyelinating disease.
Tennakoon
D K
DK
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, TX 77843, USA.
Smith
R
R
Stewart
M D
MD
Spencer
T E
TE
Nayak
M
M
Welsh
C J
CJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D018188:Cardiovirus Infections / Q000628:therapy; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000378:metabolism*; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000628:therapy; D009206:Myocardium / Q000166:cytology*; D010766:Phosphorylation; D011257:Pregnancy Proteins / Q000494:pharmacology*; D050794:STAT1 Transcription Factor; D012756:Sheep; D017945:Theilovirus / Q000187:drug effects* / Q000254:growth & development; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D006649:Histocompatibility Antigens; D007370:Interferon Type I; D011257:Pregnancy Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; C020947:interferon tau