Hepatocyte Growth Inhibitory Factor (HGI) Derived from HTLV-I (+) T cell Lines ; Effect on the Epidermal Growth Factor-dependent Proliferation of Rat Hepatocyte

在HTLV-I(+) T细胞系ATL-2的条件培养基（CM）中，我们检测到一种细胞因子可以剂量依赖性地抑制原代培养的大鼠肝细胞的表皮生长因子（EGF）依赖性增殖。细胞数量的增加和肝细胞@[^3H]-胸腺嘧啶的掺入同样被这种CM的加入所抑制。该肝细胞生长抑制因子（HGI）在分子大小15,000至40,000使用Sephacryl S-200柱分离。虽然来自同一CM的IL-2受体诱导因子ADF的活性与HGI重叠，但进一步用离子交换柱分离表明HGI与ADF不同。然而，其他HTLV-I转化的T细胞系也共同产生HGI和ADF，表明HGI和ADF呈正相关。淋巴因子如IL-2、白细胞介素-1 （IL-1）和干扰素- (IFN-)不影响肝细胞增殖。由于转化生长因子- (TGF-)对肝细胞增殖有明显的抑制作用，我们讨论HGI与TGF-的关系。提示HGI可能参与ATL患者肝功能障碍的病理生理和/或调节肝脏再生。

In the conditioned medium (CM) of an HTLV-I(+) T cell line, ATL-2, we have detected a cytokine that dose-dependently inhibits the epidermal growth factor (EGF)-dependent proliferation of primary cultured rat hepatocytes. Both the increase of cell number and @[^3H]-thymidine incorporation of the hepatocytes were similary inhibited by the addition of this CM. This hepatocyte growth inhibitory factor (HGI) was fractionated at the molecular size of 15,000 to 40,000 using a Sephacryl S-200 column. While the activity of an interleukin-2 (IL-2) receptor inducing factor derived from the same CM, ADF, was overlapping with HGI, further fractionation with ion-exchange column indicated that HGI was different from ADF. However, other HTLV-I transformed T cell lines also co-produced HGI and ADF, suggesting a positive correlation between HGI and ADF. Lymphokines such as IL-2, interleukin-1 (IL-1 ) and interferon- (IFN- ) did not affect hepatocyte proliferation. Because transforming growth factor- (TGF- ) showed a significant inhibitory activity to hepatocyte proliferation, we discuss the relationship between HGI and TGF- . The results suggested that HGI may be involved in the pathophysiology of liver dysfunction of ATL patients and/or in the ragulation of liver rageneration.