脳誘導型NOシンターゼ発現におけるチロシンキナーゼの関与 Possible involvement of tyrosine kinase activation on expression of inducible NO synthase in glial cells
To clarify the expression pathway of inducible nitric oxide synthase (iNOS) in the brain, we examined the effects of interferon-γ(IFN-γ) and lipopolysaccharide (LPS) on expression of iNOS in glial cells cultured from neonatal rats, compared to those in macrophage cell line RAW264.7. NOS activities (NO<SUB>2</SUB><SUP>-</SUP> accumulation) and l 30-kDa iNOS protein were induced 24 hr after treatment with IFN-γ or LPS in both glial cells and RAW264.7 macrophages. These expression activities was inhibited by a tyrosine kinase inhibitor, herbimycin A. From immunoprecipitation assay using antibodies against Janus kinase, IFN-γ induced tyrosinephosphorylation of Jak2 but did not induce phosphorylation of Jak 1 and Tyk2. The IFN-γ-induced-phosphorylation of Jak2 was inhibited by herbimycin A. While, LPS did not phosphorylate Janus kinase at all. These results suggest that IFN-γ-induced iNOS expression involves in the activation of Jak2 in both glial cells and macrophages. However, LPS-induced iNOS expression may involve in other kinases.
日本薬理学雑誌 106, 217-221, 1995-09-01