Interleukin 1 β markedly stimulates nitric oxide formation in the absence of other cytokines or lipopolysaccharide in primary cultured rat hepatocytes but not in Kupffer cells-猫眼课题宝

在原代培养的大鼠肝细胞中没有其他细胞因子或脂多糖的情况下，白介素 1 β 显着刺激一氧化氮的形成，但在库普弗细胞中则不然

DOI：

发表时间：

1996

期刊：

Hepatology

影响因子：

13.5

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

H. Kitade;K. Sakitani;K. Inoue;Y. Masu;N. Kawada;Y. Hiramatsu;Y. Kamiyama;T. Okumura;Seiji Ito

为了研究是否有一个单一的炎症细胞因子可以刺激一氧化氮的形成，在没有其他细胞因子或脂多糖（LPS），NO测定的氧化还原化学发光法在原代培养的大鼠肝细胞和大鼠枯否细胞。白细胞介素（IL）1 β（但IL-6、肿瘤坏死因子α（TNF-α）、干扰素γ（IFN-γ）和LPS均未以剂量依赖性方式刺激NO形成，并在30 pmol/L时诱导半数最大效应。在加入1 nmol/L IL-1 β后12 - 16小时达到最大刺激，并且是大鼠肝细胞中基础水平的50 - 60倍。还检查了这些细胞因子与LPS或IFN-γ对NO形成的联合作用。LPS和IFN-γ均不影响IL-1 β诱导的NO形成。然而，TNF-α刺激IL-1 β诱导的NO形成，而IL-6抑制它，尽管独立地这些细胞因子对NO形成没有影响。没有测试的细胞因子刺激培养的大鼠枯否细胞中NO的形成。在肝细胞中，由IL-1 β诱导的NO形成被NO合酶（NOS）抑制剂NG-单甲基-L-精氨酸（L-NMMA）和IL-1受体拮抗剂（IL-1 ra）阻断。此外，IL-1 β显著增加NOS活性，这种活性的增加伴随着诱导型NOS（iNOS）信使RNA（mRNA）的表达。这项研究清楚地表明，在没有其他细胞因子或LPS的情况下，IL-1 β显著刺激肝细胞中NO的形成。

To investigate whether a single inflammatory cytokine could stimulate nitric oxide formation in the absence of other cytokines or lipopolysaccharide (LPS), NO was measured by the redox chemiluminescence method in primary cultured rat hepatocytes and in rat Kupffer cells. Interleukin (IL) 1 beta, but neither IL‐6, tumor necrosis factor alpha (TNF‐alpha), interferon gamma (IFN‐gamma), nor LPS stimulated NO formation in a dose‐dependent manner and induced half‐maximal effects at 30 pmol/L. Maximal stimulation was achieved at 12 to 16 hours after the addition of 1 nmol/L of IL‐1 beta, and was 50‐ to 60‐fold above basal levels in rat hepatocytes. The combined effect of these cytokines with LPS or IFN‐gamma on NO formation was also examined. Neither LPS nor IFN‐gamma affected the IL‐1 beta‐induced NO formation. TNF‐alpha, however, stimulated IL‐1 beta‐induced NO formation, while IL‐6 inhibited it, although independently these cytokines had no effect on NO formation. None of the cytokines tested stimulated NO formation in cultured rat Kupffer cells. In hepatocytes, the NO formation induced by IL‐l beta was blocked by both the NO synthase (NOS) inhibitor NG‐monomethyl‐L‐arginine (L‐NMMA) and by IL‐1 receptor antagonist (IL‐1ra). Furthermore, IL‐1 beta markedly increased NOS activity, and this increase in activity was accompanied by the expression of inducible NOS (iNOS) messenger RNA (mRNA). This study clearly demonstrated that IL‐1 beta markedly stimulates NO formation in hepatocytes, in the absence of other cytokines or LPS.