|Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fluctuation of innate immunity, interferon (EFN) system and receptor (TLR) signaling pathway, was investigated in viral infected human neuronal cell lines, U118-MG (human glioblastoma), MO3.13 (human oligodendroglial cell), ST88-14 (human malignant schwannoma cell) and NT2 (cloned human embryonal carcinoma cell).
1. IFN signaling pathway:
Induction of IFN-inducible genes, oligo-2', 5'-adenylate synthetase (2-5AS) and MxA, was recognized in all of these cell lines after treatment with ITN- α, ITN- β or IFN- γ. Although these cell lines show normal response activity to WNs, induction of IFN- y signaling pathway was not found in M03.13, ST88-14 and NT2 cell lines.
Interestingly, TLR4 was induced in treatment of NT2 cells with IFN- γ in spite of no induction of 2-5AS.IFN- α / β, IFN- γ signal transduction pathway was blacked by mumps virus (MuV) infected these neuronal cell lines because of the degradation of STAT-1 and STAT-3. Furthermore, as is naturally expected, measles virus (MeV) also inhibited the IFN-α/β signaling pathway. Nevertheless the dysfunction of IFN signaling, MuV and MeV were able to induce NDA5, which invoves in IFN production, in virus infected these cell lines. It is suggested that induction of the MDA5 is dependent on viral protein (s), but not by IFNs or other cytokines.
2. TLR expression and TLR signaling pathway :
TLR3 was not found in these four neuronal cell lines, and IFNs (α, β and γ) treatment was not effectable in induction of TLR3. Expression of TLR4 was found in these cells with the exception of NT2. TLR7 was not in U118-MG. Induction of TLR4 in NT2 and TLR7 in U118-MG recovered by IFN treatment. Fluctuation of ThRs expression by virus infection was not recognized in these cell lines. Production of cytokines (IL-6, IL-8 and RANTES) by virus infection in these cell lines was lower than those in epithelium cell lines.