Takemura H, Suzuki H, Fujisawa H, Yuhara T, Akama T, Yamane K, Kashiwagi H
Department of Rheumatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
J Rheumatol. 1998 Aug;25(8):1534-9.
The pathophysiology of systemic sclerosis (SSc) is poorly understood, but recent studies indicate the involvement of cytokines in the functional changes of SSc fibroblasts. We investigated interleukin 6 (IL-6) production by dermal fibroblasts from patients with SSc.
Fibroblast cultures were established from affected skin of patients with SSc and from skin of healthy controls. IL-6 in supernatants from cultured fibroblasts was measured using a specific IL-6 ELISA.
SSc fibroblasts, starved in serum-free medium, produced only a small amount of IL-6. However, IL-6 production by SSc fibroblasts dramatically increased when the cells were cultured in serum-containing medium. Human whole blood serum was more effective than human platelet-poor plasma derived serum in the enhancement of IL-6 production by SSc fibroblasts. Platelet derived growth factor (PDGF)-AA and PDGF-BB, a major growth factor in serum, induced significant IL-6 production by SSc fibroblasts. In contrast, in normal fibroblasts, much less response to PDGF-BB and almost no response to PDGF-AA were observed. Expression of PDGF receptors on SSc fibroblasts was not significantly different from normal fibroblasts. However, IL-1 receptor antagonist (IL-1ra), when added in the medium, significantly inhibited the PDGF-induced IL-6 production by SSc fibroblasts.
PDGF stimulates IL-6 production by SSc fibroblasts. The enhanced IL-6 production in response to PDGF is due in part to autocrine IL-1 of SSc fibroblasts. These abnormalities of fibroblasts may play an important role in the inflammatory and immunological processes of SSc.
系统性硬化症（SSc）的病理生理学仍知之甚少，但最近的研究表明细胞因子参与了SSc成纤维细胞的功能变化。我们研究了SSc患者真皮成纤维细胞白细胞介素6（IL-6）的产生情况。
从SSc患者的受累皮肤和健康对照者的皮肤中建立成纤维细胞培养物。使用特异性IL-6酶联免疫吸附测定法（ELISA）测量培养的成纤维细胞上清液中的IL-6。
在无血清培养基中饥饿培养的SSc成纤维细胞仅产生少量IL-6。然而，当细胞在含血清培养基中培养时，SSc成纤维细胞的IL-6产生显著增加。人全血血清在增强SSc成纤维细胞IL-6产生方面比人少血小板血浆衍生血清更有效。血小板衍生生长因子（PDGF）-AA和血清中的主要生长因子PDGF-BB可诱导SSc成纤维细胞产生显著的IL-6。相比之下，在正常成纤维细胞中，观察到对PDGF-BB的反应少得多，对PDGF-AA几乎无反应。SSc成纤维细胞上PDGF受体的表达与正常成纤维细胞无显著差异。然而，当在培养基中添加IL-1受体拮抗剂（IL-1ra）时，可显著抑制PDGF诱导的SSc成纤维细胞IL-6产生。
PDGF刺激SSc成纤维细胞产生IL-6。对PDGF反应增强的IL-6产生部分归因于SSc成纤维细胞的自分泌IL-1。成纤维细胞的这些异常可能在SSc的炎症和免疫过程中起重要作用。
