Gu Z J, Costes V, Lu Z Y, Zhang X G, Pitard V, Moreau J F, Bataille R, Wijdenes J, Rossi J F, Klein B
Institute for Molecular Genetics, Montpellier, France.
Blood. 1996 Nov 15;88(10):3972-86.
We have a previously reported that interleukin-10 (IL-10) is a potent but IL-6-unrelated growth factor for freshly explanted myeloma cells (Lu et al, Blood 85:2521, 1995). We have also shown that exogenous IL-10 supported the growth of XG-1 and XG-2 human myeloma cell lines (HMCL) through an IL-6-independent mechanism. (Lu et al, Blood 85:2521, 1995). Because the IL-10 receptor does not involve the gp 130 IL-6 transducer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth factor activity of IL-10 was abrogated by an antibody to the gp 130 IL-6 transducer, indicating that it was mediated through one of the gp 130-activating cytokines. We found that myeloma cells from XG-1 and XG-2 HMCL and from 5 of 6 patients' tumoral samples produced oncostatin M (OM) constitutively but failed to produce IL-6, IL-11 and leukemia-inhibitory factor (LIF). The autocrine OM was inactive in the absence of IL-10 due to lack of a functional OM receptor on myeloma cells. IL-10, by inducing the receptor for LIF (LIFR), produced a functional autocrine OM loop in XG-1 and XG-2 cells and in primary myeloma cells from 2 patients. We also found that some myeloma cell lines (XG-4, XG-6, and XG-7) an fresh myeloma cells from 3 of 6 patients produced an autocrine IL-10 and that these cells constitutively expressed LIFR. One HMCL (XG-7) produced IL-10, OM, and IL-6 an expressed LIFR. The XG-7 cells used OM and IL-6 as autocrine growth factors. We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995). Taken together, these results show that IL-10 is a key cytokine for inducing the expression of LIFR and IL-11R and possibly another uncharacterized OM coreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factors reported to data involve an activation of the gp130 IL-6 transducer.
我们之前曾报道白细胞介素-10（IL-10）是一种对新分离的骨髓瘤细胞有强大作用但与IL-6无关的生长因子（Lu等人，《血液》85:2521，1995）。我们还表明外源性IL-10通过一种不依赖IL-6的机制支持XG-1和XG-2人骨髓瘤细胞系（HMCL）的生长（Lu等人，《血液》85:2521，1995）。由于IL-10受体不涉及gp130 IL-6转导分子，我们试图阐明IL-10对骨髓瘤细胞的作用机制。我们的结果表明，针对gp130 IL-6转导分子的抗体可消除IL-10的骨髓瘤细胞生长因子活性，这表明其作用是通过一种激活gp130的细胞因子介导的。我们发现XG-1和XG-2 HMCL以及6例患者肿瘤样本中的5例的骨髓瘤细胞组成性地产生制瘤素M（OM），但不产生IL-6、IL-11和白血病抑制因子（LIF）。由于骨髓瘤细胞上缺乏功能性OM受体，自分泌的OM在没有IL-10时无活性。IL-10通过诱导LIF受体（LIFR），在XG-1和XG-2细胞以及2例患者的原发性骨髓瘤细胞中产生了一个功能性的自分泌OM环路。我们还发现一些骨髓瘤细胞系（XG-4、XG-6和XG-7）以及6例患者中3例的新鲜骨髓瘤细胞产生自分泌IL-10，并且这些细胞组成性地表达LIFR。一个HMCL（XG-7）产生IL-10、OM和IL-6并表达LIFR。XG-7细胞将OM和IL-6用作自分泌生长因子。我们之前曾表明IL-10可诱导骨髓瘤细胞中的IL-11受体并使其对IL-11敏感（Lu等人，《欧洲生物化学学会联合会快报》377:515，1995）。综上所述，这些结果表明IL-10是诱导骨髓瘤细胞中LIFR和IL-11R以及可能另一种未鉴定的OM共受体表达的关键细胞因子，并且OM和IL-10可能由骨髓瘤细胞产生。它们还强调，迄今为止报道的所有骨髓瘤细胞生长因子都涉及gp130 IL-6转导分子的激活。
