Cytokine induction of NO synthase II in human DLD-1 cells: roles of the JAK-STAT, AP-1 and NF-κB-signaling pathways

摘要

In human epithelial-like DLD-1 cells, nitric oxide synthase(NOS) II expression was induced by interferon-γ(100 u ml~-1) alone and, to a larger extent, by a cytokine mixture(CM) consisting of interferon-γ, iterleukin-1β(50 u ml~-1) and tumor necrosis factor-α(10 ng ml~-1). CM-induced NOS II expression was inhibited by tyrphostin B42 (mRNA down to 1/100; nitrite Production down to 0.5/100 at 300 μM) and tyrphostin A25 (mRNA down to 24/100, nitrite production Down to 1/100 at 200 μM), suggesting the involvement of janus kinase 2 (JAK-2). Tyrphostin B42 also Blocked the CM-induced JAK-2 phosphorylation(kinase assay) and reduced the CM-stimulated STAT1α binding activity(gel shift analysis).