Study on interleukin 1 signal transduction

IL-1在宿主的免疫、炎症和血液学反应中发挥重要作用，并调节细胞增殖和分化。在本研究中，我们分析了IL-1信号传导导致人类黑色素瘤细胞增殖抑制的机制。（A375.1）IL-1似乎通过增加鸟氨酸脱羧酶（ODC）的调节因子AZ来抑制细胞增殖，无论是转录水平还是后转录水平，而不是移码。IL-1还上调p38MAPK的活性，从而在转录后水平上调控AZ的水平。细胞周期调节因子p53、p21和p16的表达水平以及Rb的磷酸化水平均不受IL-1的影响。1.2)通过IL-1敏感细胞和IL-1耐药细胞杂交发现，对IL-1的抗性是隐性的。相比之下，在IL-1抗性细胞中观察到的IL-1 α和IL-6的组成性产生占主导地位。因此，在耐药细胞中，导致il -1诱导的细胞增殖抑制的信号是缺乏的。3)与敏感细胞相比，IL-1耐药细胞的细胞粘附分子、IL-8和基质金属蛋白酶的产生、对基质的侵袭性等已报道的人类黑色素瘤恶性特征均有所增加。因此，IL-1耐药细胞似乎是研究人类黑色素瘤恶性机制的一个很好的模型。4) LPS可提高小鼠肝脏中IL-1RI mRNA的表达水平。在该模型中，IL-1、IL-6和糖皮质激素（GC）似乎发挥了重要作用。GC和IL-6均可增加肝细胞表面IL-1RI分子的数量。

IL-1 plays an important role in host reactions, including immunologic, inflammatory and hematologic reactions, and in regulation of cell proliferation and differentiation. In this study we analyzed the mechanism of IL-1 signaling leading to the inhibition of cell proliferation of human melanoma cells A375.1)IL-1 appeared to inhibit the cell proliferation by an increase of AZ,a reguratory factor of ornithine decarboxylase (ODC), both in the levels of transcription and posttranscription other than frameshift. IL-1 also upregulated the activity of p38MAPK which regulated AZ level at the level of posttranscription. The expression levels of cell cycle-regulatory factors, p53, p21 and p16, as well as phosphorylation levels of Rb were not influenced by IL-1.2)By cell hybridization between IL-1 sensitive and resistant cells, resistance to IL-1 appeared to be recessive. In contrast, the constitutive production of IL-1alpha and IL-6 observed in IL-1 resistant cells was dominant. Therefore, in resistant cells the signaling leading to IL-1-induced inhibition of cell proliferation is deficient.3)The characteristics of reported malignant characteristics in human melanoma, including cell adhesion molecules, production of IL-8 and matrix metalloproteinases, invasiveness into matrigel were all incresed in IL-1 resistant cells compared to those of sensitive cells. Therefore, the IL-1 resistant cells apperaed to be a very good model to investigate the mechanism of malignancy of human melanomas.4)By administration of LPS into mice, the expression level of IL-1RI mRNA in the liver was augmented. In this model, IL-1, IL-6 and glucocorticoid (GC) appeared to play an important role. Furthermore, the number of IL-1RI molecule on the cell surface of hepatocytes was increased by treatment with GC and IL-6.