Kleinerman E S, Lachman L B, Knowles R D, Snyderman R, Cianciolo G J
Department of Cell Biology, University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston 77030.
J Immunol. 1987 Oct 1;139(7):2329-37.
The synthetic peptide CKS-17 has homology to a highly conserved region of the immunosuppressive retroviral envelope protein P15E, to envelope proteins of HTLV I, II, III, and to that encoded by an endogeneous C-type human retroviral DNA. CKS-17 inhibits the immune response of lymphocytes and the respiratory burst of human monocytes. Because P15E-related antigens are present in human malignant cell lines and cancerous effusions, we sought to determine the effect of CKS-17 on monocyte-mediated tumor cell lysis. Lysis of A375 tumor cells by lymphokine or lipopolysaccharide-activated human monocytes was inhibited by 10 microM CKS-17 (control, 79%; CKS-17-treated, 19%). Another synthesized peptide, CS-2, which has partial homology to CKS-17, failed to block monocyte-mediated killing. Thus, the inhibition by CKS-17 appeared to be specific. Because interleukin 1 (IL-1) is a cytocidal factor produced by activated monocytes, we also investigated the effect of CKS-17 on IL-1 production by monocytes and on direct IL-1-mediated cytotoxicity. CKS-17 did not block production or secretion of IL-1 by lipopolysaccharide- or interferon-gamma-activated monocytes. However, the direct cytocidal activity of both recombinant IL-1 alpha and IL-1 beta against A375 tumor cells was blocked by CKS-17. The cytotoxic activity of IL-1 was inhibited by CKS-17 if (a) IL-1 was preincubated with CKS-17 for 1 hr at 37 degrees C or (b) the A375 cells were incubated with CKS-17 for 1 hr prior to the addition of IL-1. CKS-17 also blocked IL-1-induced proliferation of murine thymocytes, the D10 T cell line, and an IL-1-responsive astrocytoma cell line. These data suggest that CKS-17 may be a potent inhibitor of IL-1.
合成肽CKS - 17与免疫抑制逆转录病毒包膜蛋白P15E的一个高度保守区域具有同源性，与HTLV I、II、III的包膜蛋白以及由内源性C型人类逆转录病毒DNA编码的蛋白具有同源性。CKS - 17可抑制淋巴细胞的免疫反应和人类单核细胞的呼吸爆发。由于P15E相关抗原存在于人类恶性细胞系和癌性积液中，我们试图确定CKS - 17对单核细胞介导的肿瘤细胞裂解的影响。10微摩尔的CKS - 17可抑制淋巴因子或脂多糖激活的人类单核细胞对A375肿瘤细胞的裂解（对照，79%；CKS - 17处理组，19%）。另一种与CKS - 17具有部分同源性的合成肽CS - 2未能阻断单核细胞介导的杀伤作用。因此，CKS - 17的抑制作用似乎具有特异性。由于白细胞介素1（IL - 1）是活化单核细胞产生的一种细胞杀伤因子，我们还研究了CKS - 17对单核细胞产生IL - 1以及对直接的IL - 1介导的细胞毒性的影响。CKS - 17不会阻断脂多糖或干扰素 - γ激活的单核细胞产生或分泌IL - 1。然而，重组IL - 1α和IL - 1β对A375肿瘤细胞的直接细胞杀伤活性被CKS - 17阻断。如果（a）IL - 1与CKS - 17在37℃下预孵育1小时，或者（b）在加入IL - 1之前，将A375细胞与CKS - 17孵育1小时，IL - 1的细胞毒性活性会被CKS - 17抑制。CKS - 17还可阻断IL - 1诱导的小鼠胸腺细胞、D10 T细胞系以及IL - 1反应性星形细胞瘤细胞系的增殖。这些数据表明CKS - 17可能是一种有效的IL - 1抑制剂。
