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Purpose : Insulin-like growth factor 1 (IGF-1) elicits multiple biological responses, such as growth, differentiation, and metabolism of various cells, through its high- affinity binding to IGF-1 receptor (IGF-1R). IGF-1 and IGF-1R have been implicated in the development thyroid-associated ophthalmopathy (TAO). In the current study, we investigated the issue of whether how orbital fibroblasts (OFs) from TAO patients significantly secret higher level of IGF-1.
Methods : Human orbital fibroblasts were obtained from orbital fat from patients with TAO who underwent orbital decompression (n = 6) or from patients who had upper lid blepharoplasty with no prior history of thyroid disease (n = 6). The IGF-1 level in culture media of OFs was determined by using an ELISA kit. The IGF-1 mRNA level of OFs was determined by quantitative real-time RT-PCR. The NF-kB activity of OFs was determined by measuring the level of IkB degradation and IKKa/IKKb phosphorylation.
Results : Cultured OFs from TAO patients significantly secreted higher level of IGF-1 (303 pg/ml), compared with those of control groups (142 pg/ml). IGF-1 mRNA by OFs in TAO patients was up-regulated more than 27-fold compared with control groups (P<0.05). In addition, the levels of IkB degradation and IKKa/IKKb phosphorylation were higher in OFs of TAO patients than those of control groups. Furthermore, treatment with Bay 11-7082, an inhibitor of NF-kB, reduced the levels of IGF-1 secretion and IGF-1 mRNA expression in OFs from TAO patients.
Conclusion : These results suggest that IGF-1 expression is dependent on NF-kB activation pathway in OFs from TAO patients. These findings also show that NF-kB/IGF-1 pathway may be a reasonable target of therapeutic intervention in the case of TAO.
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