The mechanism and its regulation of interleukin 1 biological activities

IL-1在宿主反应中发挥重要作用，包括免疫、炎症和血液学反应，并在细胞增殖和分化调节中发挥重要作用。本研究试图阐明(A)IL-1信号转导抑制人黑色素瘤A375细胞增殖的机制，(B)IL-1受体(IL-1R)及其家族在体内外表达的调控机制。(1)IL-1在翻译水平上调鸟氨酸脱羧酶(ODC)调节因子AZ的蛋白水平，在AZ的mRNA2序列中存在IL-1反应区。2)CHOP通过增强IL-6的转录参与了IL-1的抗增殖作用。3)CHOP增强了多种因子的转录活性，包括核因子-IL-6、AP-1、5)CHOP对IL-1敏感的A375-6细胞和IL-1抵抗的A375-R8细胞的增殖均有抑制作用。在这两个细胞克隆中均观察到依赖p38MAPK的肿瘤坏死因子抑制增殖通路，而仅在R8细胞中观察到非依赖于p38MAPK的凋亡通路。这种半衰期很短的抗凋亡因子在A375-6细胞中存在，而在R8细胞中不存在。

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 attempted to clarify (A) the mechanism of IL-1 signaling leading to the inhibition of cell proliferation of human melanoma cells A375, (B) the regulatory mechanism of expression of IL-1 receptor (IL-1R) and its family in vitro and in vivo. The following points have been clarified.(A)1) It was suggested that IL-1 up-regulated the protein level of AZ, a reguratory factor of ornithine decarboxylase (ODC), at translational level, and IL-1 responsive region was present within the sequence of AZ mRNA.2) CHOP contributed to the antiproliferative effect of IL-1 by augmenting IL-6 transcription3) CHOP augmented the transcriptional activity of many factors, including NF-IL-6, AP-1, ISRE and NF-κB.4) CHOP also appeared to stabilize the protein levels of other C/EBP family members.5) TNF inhibited the proliferation of both IL-1 sensitive A375-6 cells and IL-1 resistant A375-R8 cells. The p38MAPK-dependent antiproliferative pathway of TNF was observed in these two cell clones however p38MAPK-independent apoptosis pathway was observed in only R8 cells. The anti-apoptosis factor with very short half life appeared to be present in A375-6 cells but not in R8 cells.