Girard N, Maingonnat C, Bertrand P, Vasse M, Delpech B
Laboratoire d'oncologie moléculaire, Université de Rouen, Rouen, France.
Cytokine. 1999 Aug;11(8):579-84. doi: 10.1006/cyto.1998.0461.
Hyaluronectin (HN) is a component of the extracellular matrix of connective tissue and is particularly associated with tumour inflammatory and connective stroma reaction, where it co-localizes with hyaluronic acid (HA). The HN/HA ratio has been suggested to be involved in tumour aggressivity and in the atherosclerosis process. IL-10 has also been described in atherosclerotic lesions and in cancer. HN production was therefore investigated in vitro in peripheral blood monocyte cell (PBMC) cultures, with and without bacterial lipolysaccharide (LPS) or interleukins (ILs) in the medium. HN was characterized in monocytic cell cytoplasm and in culture supernatants. Anti-IL-10 antibody suppressed the LPS-stimulating effect on HN production. HN synthesis rate was greatly increased in IL-10-activated cultures while IL-4 and IL-13, two other anti-inflammatory ILs, decreased HN release. In the presence of IL-10, the IL-4 or Il-13 inhibitory effect on HN synthesis was reversed. The results support the view that intratumoral release of IL-10 by monocytes may induce local production of HN. In conjunction with the known ability of HN to bind to HA, which is a cell migration and tumour invasion facilitating factor, and to inhibit HA-induced angiogenesis, our findings suggest that HN may modulate the effect of HA on atherosclerosis, angiogenesis and cancer development.
透明质连接素（HN）是结缔组织细胞外基质的一个组成部分，尤其与肿瘤炎症及结缔组织基质反应相关，在该反应中它与透明质酸（HA）共同定位。有人提出HN/HA比值与肿瘤侵袭性及动脉粥样硬化进程有关。白细胞介素-10（IL-10）在动脉粥样硬化病变及癌症中也有报道。因此，我们在体外研究了外周血单核细胞（PBMC）培养物中HN的产生情况，培养基中分别添加或不添加细菌脂多糖（LPS）或白细胞介素（ILs）。对单核细胞胞质及培养上清液中的HN进行了特性分析。抗IL-10抗体抑制了LPS对HN产生的刺激作用。在IL-10激活的培养物中，HN合成率大幅增加，而另外两种抗炎性白细胞介素IL-4和IL-13则降低了HN的释放。在存在IL-10的情况下，IL-4或IL-13对HN合成的抑制作用被逆转。这些结果支持了这样一种观点，即单核细胞在肿瘤内释放IL-10可能诱导HN的局部产生。结合HN已知的与HA结合的能力（HA是一种促进细胞迁移和肿瘤侵袭的因子）以及抑制HA诱导的血管生成的能力，我们的研究结果表明，HN可能调节HA对动脉粥样硬化、血管生成及癌症发展的影响。
