Constitutive cytokine production by primary effusion (body cavity-based) lymphoma-derived cell lines
Constitutive cytokine production by primary effusion (body cavity-based) lymphoma-derived cell lines
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DOI：
10.1038/sj.leu.2401371
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发表时间：
1999-04-01
期刊：
影响因子：
11.4
通讯作者：
Carbone, A
中科院分区：
文献类型：
--
作者：
Drexler, HG;Meyer, C;Carbone, A
原发性渗出性淋巴瘤（PEL）是一种新的淋巴瘤实体，主要发生在艾滋病毒阳性的获得性免疫缺陷综合征（AIDS）患者中，但不限于此。PEL仅在体腔内生长，表现为浆液性淋巴瘤性渗出，无肿块或播散的证据。这些细胞被新发现的人类疱疹病毒-8（HHV-8）感染，通常伴有EB病毒（EBV）的共同感染。已经从患有AIDS和非AIDS相关的PEL的患者建立了几种淋巴瘤细胞系。鉴于其与浆细胞的表型关系，几种细胞因子可能对PEL细胞的生长和存活很重要。我们研究了9种HHV-8+ PEL细胞系产生的细胞因子谱，并与5种伯基特淋巴瘤、7种其他B非霍奇金淋巴瘤（B-NHL）和7种多发性骨髓瘤衍生细胞系进行了比较。此外，我们测试了PEL细胞对所选细胞因子的反应以及中和抗细胞因子和抗细胞因子受体抗体的作用。使用特异性ELISA，发现PEL细胞系产生大量的白细胞介素-6（IL-6; 10-5000 pg/ml），IL-6可溶性受体（IL-6sR; 30-600 pg/ml）、IL-10（600-80 000 pg/ml）和制瘤素M（OSM; 50-80 pg/ml），其在大多数情况下显著高于Burkitt、B-NHL或骨髓瘤细胞系产生的水平;相反，PEL细胞系不产生显著水平的巨噬细胞抑制蛋白（MIP-1 α）和白血病抑制因子（LIF）。然而，MIP-1 α的水平通过用佛波醇酯TPA治疗增加了10至100倍。BEL细胞系对IL-6、IL-10、IL-11、LIF、MIP-1 α或OSM没有增殖反应。与IL-6sR和IL-6孵育抑制细胞生长。抗-IL 6中和抗体对PEL细胞系增殖没有影响;相反，尽管单独的抗-IL 6 R仅微弱地抑制，但抗-gp 130和抗-gp 130加抗-IL 6 R显示出强的抑制作用（在5/9个细胞系中>20%的抑制和在3/9个细胞系中>60%的抑制）。总之，PEL细胞系产生大量细胞因子（IL-6、IL-10、OSM）;通过阻断IL-6信号传导途径的受体可抑制增殖。
Primary effusion lymphoma (PEL) is a new lymphoma entity occurring predominantly, but not exclusively in HIV+ patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. The cells are infected with the newly discovered human herpesvirus-8 (HHV-8), often accompanied by co-infection with Epstein-Barr virus (EBV). Several lymphoma cell lines have been established from patients with AIDS- and non-AIDS-associated PEL. Given their phenotypical relationship to plasma cells, several cytokines may be important for growth and survival of PEL cells. We investigated the spectrum of cytokines produced by nine HHV-8+ PEL cell lines, in comparison with five Burkitt lymphoma, seven other B non-Hodgkin's lymphoma (B-NHL) and seven multiple myeloma-derived cell lines. In addition, we tested the response of the PEL cells to selected cytokines and the effects of neutralizing anti-cytokine and anti-cytokine receptor antibodies. Using specific ELISAs, PEL cell lines were found to produce large amounts of interleukin-6 (IL-6; 10-5000 pg/ml), IL-6 soluble receptor (IL-6sR; 30-600 pg/ml), IL-10 (600-80 000 pg/ml) and oncostatin M (OSM; 50-80 pg/ml) which in most cases were significantly higher than the levels produced by the Burkitt, B-NHL or myeloma cell lines; on the contrary, PEL cell lines did not elaborate significant levels of macrophage inhibitory protein (MIP-1 alpha) and leukemia inhibitory factor (LIF). However, the levels of MIP-1 alpha were increased 10- to 100-fold by treatment with phorbol ester TPA. PEL cell lines did not respond proliferatively to IL-6, IL-10, IL-11, LIF, MIP-1 alpha, or OSM. Incubation with IL-6sR and IL-6 inhibited cell growth. Anti-IL6 neutralizing antibodies had no effect on PEL cell line proliferation; conversely, whereas anti-IL6R alone inhibited only weakly, anti-gp130 and anti-gp130 plus anti-IL6R showed strong inhibitory effects (>20% inhibition in 5/9 lines and >60% inhibition in 3/9 lines). In summary, PEL cell lines produce high amounts of cytokines (IL-6, IL-10, OSM); proliferation could be inhibited by blocking the receptors of the IL-6 signaling pathway.