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

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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.

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  • 日本薬理学雑誌

    日本薬理学雑誌 106, 217-221, 1995-09-01

    公益社団法人 日本薬理学会

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