Masood R, Zhang Y, Bond M W, Scadden D T, Moudgil T, Law R E, Kaplan M H, Jung B, Espina B M, Lunardi-Iskandar Y
Department of Medicine, University of Southern California, Norris Cancer Hospital and Research Institute, Los Angeles 90033, USA.
Blood. 1995 Jun 15;85(12):3423-30.
Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL-10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombinant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL-10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis.
白细胞介素-10(IL-10)是一种35kD的酸敏感蛋白,具有多种效应,包括抑制细胞毒性T细胞反应、诱导B淋巴细胞中II类主要组织相容性复合体、诱导B细胞生长和分化以及单核细胞中的自分泌生长因子活性。我们和其他人已经表明,IL-10由人类免疫缺陷病毒血清阳性患者的血液单核细胞自发产生。为了确定IL-10在获得性免疫缺陷综合征(AIDS)相关B细胞淋巴瘤中的潜在作用,我们评估了人类IL-10在肿瘤来源的B细胞系和原发性肿瘤细胞中的表达。在所检测的五个细胞系中的四个中检测到了人类IL-10(hIL-10)mRNA和蛋白的表达。一种IL-10反义寡核苷酸抑制了IL-10 mRNA表达和IL-10蛋白产生。反义寡核苷酸以剂量依赖的方式抑制了所有B细胞系的增殖,添加重组hIL-10蛋白可消除这种抑制作用。在不产生hIL-10的B细胞系中未观察到反义寡核苷酸的作用。对AIDS淋巴瘤患者的原发性肿瘤细胞的评估显示,其对IL-10的产生和反应相似。这些数据提示IL-10在AIDS相关淋巴瘤细胞中存在自分泌生长机制,并且IL-10可能在其发病机制中起重要作用。