Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani A
Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy.
Immunity. 1997 Mar;6(3):315-25. doi: 10.1016/s1074-7613(00)80334-9.
IL-6-/- mice showed impaired leukocyte accumulation in subcutaneous air pouches. Defective leukocyte accumulation was not due to a reduced migratory capacity of IL-6-/- leukocytes and was associated with a reduced in situ production of chemokines. These observations led to a reexamination of the interaction of IL-6 with endothelial cells (EC). EC express only the gp130 signal transducing chain and not the subunit-specific IL-6R and are therefore unresponsive to IL-6. However, EC are responsive to a combination of IL-6 and soluble IL-6R as measured by the activation of STAT3, chemokine expression, and augmentation of ICAM-1. Activation by IL-6-IL-6R complexes was inhibited by an IL-6 receptor antagonist and potentiated by a superagonist. Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment.
IL-6基因敲除小鼠皮下气囊中的白细胞聚集受损。白细胞聚集缺陷并非由于IL-6基因敲除白细胞的迁移能力降低，而是与趋化因子原位产生减少有关。这些观察结果促使人们重新审视IL-6与内皮细胞（EC）之间的相互作用。EC仅表达gp130信号转导链，而不表达亚基特异性IL-6受体，因此对IL-6无反应。然而，通过STAT3激活、趋化因子表达和ICAM-1增加来衡量，EC对IL-6和可溶性IL-6R的组合有反应。IL-6受体拮抗剂可抑制IL-6-IL-6R复合物的激活，而超激动剂可增强其激活。因此，体内和体外证据支持这样一种概念，即IL-6系统通过放大白细胞募集在局部炎症反应中发挥意想不到的积极作用。
