Orbital fibroblasts from thyroid‐associated ophthalmopathy patients secret IL‐6 via up‐regulation of IGF‐1 by activating the NF‐kB pathway

Abstract

AbstractPurposeInterleukin (IL)‐6 plays as a modulator for functions of lymphocytes. Significantly higher level of IL‐6 has been observed in primary orbital tissue cultures of thyroid‐associated ophthalmopathy (TAO) patients compared to those of non‐TAO patients. In the current study, we investigated the issue of whether of how orbital fibroblasts (OFs) from TAO patients significantly secret higher level of IL‐6.MethodsHuman OFs were obtained from orbital fat from decompression surgery in patients with TAO or from upper lid blepharoplasties in patients with no prior history of thyroid disease. The levels of IL‐6 and insulin‐like growth factor (IGF)‐1 in culture media of OFs were determined by using an ELISA kit. The NF‐kB activity of OFs was determined by measuring the level of IkB degradation and IKKa/ IKKb/NF‐kBp65 phosphorylation.ResultsCultured OFs from TAO patients significantly secreted higher level of IL‐6 and IGF‐1, compared with those of control groups. In addition, treatment with IGF‐1 induced secretion of IL‐6 in OFs from TAO patients. The levels of IkB degradation and IKKa/IKKb/NF‐kBp65 phosphorylation were higher in non‐treated OFs of TAO patients than those of control groups. Furthermore, treatment with Bay 11‐7082, an inhibitor of NF‐kB pathway, reduced the secretion of IL‐6 and IGF‐1 in OFs from TAO patients.ConclusionsThese results suggest that IL‐6 secretion is dependent on NF‐kB/IGF‐1 pathway in OFs from TAO patients. These findings also show that NF‐kB/IGF‐1/IL‐6 pathway may be a reasonable target of therapeutic intervention in the case of TAO.