Motta Juliana Maria, Sperandio Aline, Castelo-Branco Morgana Teixeira Lima, Rumjanek Vivian Mary
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Hum Immunol. 2014 Jul;75(7):641-9. doi: 10.1016/j.humimm.2014.04.013. Epub 2014 Apr 24.
Professional antigen-presenting cells, dendritic cells (DCs) play an important role in controlling tumors. It is known that solid tumor cell products inhibit DC differentiation. Recently a similar effect produced by leukemic cell products has been demonstrated. In this case, leukemic cell products induced the secretion of IL-1β by monocytes undergoing differentiation. The aim of the present work was to characterize and to compare the development of monocyte-derived DCs under the influence of leukemic cell products (K562 supernatant) or exogenous IL-1β. It became clear that leukemic cell products and IL-1β differentially modulate some of the parameters studied on monocytes stimulated to differentiate into DCs. In the presence of K562 supernatant, the expression of the macrophage markers CD16 and CD68 were higher than in immature DCs control. Contrasting with IL-1β, leukemic cell products possibly favor the development of cells with macrophage markers. In addition, CD80 and CD83 expressions were also higher in the presence of tumor supernatant whereas HLA-DR was lower. In the presence of IL-1β, only CD80 was increased. Furthermore, it was observed that when monocytes were induced to differentiate into DCs in the presence of tumor supernatant and then activated, they expressed less CD80 and CD83 than activated DCs control. A reduced expression of CD83 following activation was also seen in cells differentiated with IL-1β. TGF-β and VEGF were found in the tumor supernatants. Moreover, the exposure to tumor supernatant or IL-1β stimulated IL-10 production while decreased IL-12 production by activated DCs. Finally, these results suggest that the addition of products released by leukemic cells or, more discreetly, the addition of IL-1β affects DC differentiation, inducing a suppressive phenotype.
专业抗原呈递细胞——树突状细胞（DCs）在控制肿瘤方面发挥着重要作用。已知实体瘤细胞产物会抑制DC分化。最近，白血病细胞产物也显示出类似的作用。在这种情况下，白血病细胞产物可诱导正在分化的单核细胞分泌IL-1β。本研究的目的是表征和比较在白血病细胞产物（K562上清液）或外源性IL-1β影响下单核细胞来源的DCs的发育情况。结果表明，白血病细胞产物和IL-1β对刺激分化为DCs的单核细胞所研究的一些参数有不同的调节作用。在K562上清液存在的情况下，巨噬细胞标志物CD16和CD68的表达高于未成熟DCs对照组。与IL-1β相反，白血病细胞产物可能有利于具有巨噬细胞标志物的细胞的发育。此外，在肿瘤上清液存在的情况下，CD80和CD83的表达也较高，而HLA-DR较低。在IL-1β存在的情况下，只有CD80增加。此外，观察到当单核细胞在肿瘤上清液存在的情况下被诱导分化为DCs然后被激活时，它们表达的CD80和CD83比激活的DCs对照组少。在用IL-1β分化的细胞中，激活后CD83的表达也降低。在肿瘤上清液中发现了TGF-β和VEGF。此外，暴露于肿瘤上清液或IL-1β会刺激IL-10的产生，同时降低激活的DCs产生IL-12的量。最后，这些结果表明，白血病细胞释放的产物的添加，或者更谨慎地说，IL-1β的添加会影响DC分化，诱导出抑制性表型。
