|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
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.