Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells.
Interferon-gamma and NF-kappaB mediate nitric oxide production by mesenchymal stromal cells.
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DOI：
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发表时间：
2007
影响因子：
3.1
通讯作者：
I. Oh;K. Ozaki;K. Sato;A. Meguro;R. Tatara;K. Hatanaka;T. Nagai;K. Muroi;K. Ozawa
中科院分区：
文献类型：
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作者：
I. Oh;K. Ozaki;K. Sato;A. Meguro;R. Tatara;K. Hatanaka;T. Nagai;K. Muroi;K. Ozawa
间充质基质细胞（MSCs）已被证明具有免疫抑制作用。先前，我们证明了一氧化氮（NO）是间充质干细胞的免疫调节介质之一。我们在此表明，原代小鼠骨髓间充质干细胞和三种模拟间充质干细胞的细胞系在Th1条件下抑制分化和增殖，而在Th2条件下抑制是轻微的。在Th1和Th2条件下，NO的产生与T细胞增殖呈负相关。NO在Th1中被高度诱导，在Th2中被最低限度诱导。此外，NO合成酶抑制剂可以恢复Th1条件下的增殖和干扰素γ (ifn - γ)的产生。此外，抗ifn - γ抗体强烈抑制NO的产生，NF-kappaB抑制剂降低MSCs中诱导NO合成酶（iNOS）的诱导水平。综上所述，我们的研究结果表明，NO在MSCs对Th1和Th2分化的修饰中起着重要作用，ifn - γ和NF-kappaB对MSCs产生NO至关重要。
Mesenchymal stromal cells (MSCs) have been shown to have an immunosuppressive effect. Previously, we demonstrated that nitric oxide (NO) is one of the immunomodulatory mediators of MSCs. We herein show that primary mouse bone marrow MSCs and three cell lines that mimic MSCs suppress both differentiation and proliferation in Th1 condition, whereas the suppression in Th2 condition is mild. NO production is inversely correlated with T cell proliferation in Th1 and Th2 conditions. NO is highly induced in Th1 and minimally induced in Th2. Moreover, an inhibitor of NO synthase restores both proliferation and interferon-gamma (IFN-gamma) production in Th1 condition. Furthermore, an anti-IFN-gamma antibody strongly inhibits NO production and an inhibitor of NF-kappaB reduces the level of induction of inducible NO synthase (iNOS) in MSCs. Taken together, our results suggest that NO plays a significant role in the modification of Th1 and Th2 differentiation by MSCs, and that both IFN-gamma and NF-kappaB are critical for NO production by MSCs.