Metcalfe R A, Weetman A P
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital, UK.
Clin Endocrinol (Oxf). 1994 Jan;40(1):67-72. doi: 10.1111/j.1365-2265.1994.tb02445.x.
Smoking is a risk factor for the development of thyroid-associated ophthalmopathy, an inflammatory process primarily affecting the fibroblasts in extraocular muscles. We wished to determine whether the extraocular muscle fibroblasts are more sensitive than dermal fibroblasts to T-cell derived cytokines, as a reason for this anatomical localization, and whether hypoxia alters fibroblast function, as one explanation for the susceptibility conferred by smoking.
Fibroblasts derived from the skin or extraocular muscles of healthy subjects were cultured with cytokines under normal (5% CO2:95% air) and hypoxic (5% CO2:95% N2) conditions.
Glycosaminoglycan, protein and DNA synthesis were measured by assessing incorporation of D-6-3H-glucosamine, 3H-amino acids, and 3H-thymidine respectively.
alpha-interferon and interleukin-6 had no effect on fibroblasts. gamma-interferon, tumour necrosis factor and interleukin-1 stimulated glycosaminoglycan synthesis; this effect was greater in orbital than in dermal fibroblasts with gamma-interferon and interleukin-1 (P < 0.05). The same cytokines stimulated total protein with a greater response in orbital fibroblasts with gamma-interferon. Interleukin-1 inhibited DNA synthesis in orbital fibroblasts but stimulated DNA synthesis in dermal fibroblasts (P < 0.01); tumour necrosis factor also displayed a differential effect (P < 0.01). Hypoxia caused a significant increase in glycosaminoglycan, protein and DNA synthesis in both types of fibroblasts, under both basal and cytokine-treated conditions (P < 0.05).
Extraocular muscle fibroblasts respond differently from dermal fibroblasts following cytokine stimulation, which may explain in part the anatomical localization of ophthalmopathy. Hypoxia stimulates fibroblasts and this could contribute, as an enhancing factor, to the adverse effects of smoking on thyroid eye disease.
吸烟是甲状腺相关眼病发生的一个危险因素，这是一种主要影响眼外肌成纤维细胞的炎症过程。我们想要确定眼外肌成纤维细胞是否比真皮成纤维细胞对T细胞衍生的细胞因子更敏感，以此作为这种解剖学定位的一个原因，以及低氧是否会改变成纤维细胞功能，作为吸烟所致易感性的一种解释。
将来自健康受试者皮肤或眼外肌的成纤维细胞在正常（5%二氧化碳：95%空气）和低氧（5%二氧化碳：95%氮气）条件下与细胞因子一起培养。
分别通过评估D-6-3H-葡萄糖胺、3H-氨基酸和3H-胸腺嘧啶核苷的掺入来测量糖胺聚糖、蛋白质和DNA合成。
α-干扰素和白细胞介素-6对成纤维细胞无影响。γ-干扰素、肿瘤坏死因子和白细胞介素-1刺激糖胺聚糖合成；γ-干扰素和白细胞介素-1作用下，眼眶成纤维细胞的这种作用比真皮成纤维细胞更强（P<0.05）。相同的细胞因子刺激总蛋白合成，γ-干扰素作用下眼眶成纤维细胞的反应更强。白细胞介素-1抑制眼眶成纤维细胞的DNA合成，但刺激真皮成纤维细胞的DNA合成（P<0.01）；肿瘤坏死因子也表现出不同的作用（P<0.01）。在基础和细胞因子处理条件下，低氧均导致两种类型成纤维细胞的糖胺聚糖、蛋白质和DNA合成显著增加（P<0.05）。
细胞因子刺激后，眼外肌成纤维细胞与真皮成纤维细胞的反应不同，这可能部分解释了眼病的解剖学定位。低氧刺激成纤维细胞，这可能作为一个增强因素，导致吸烟对甲状腺眼病产生不良影响。
