Abstract
Steroid applications are able to repress inflammatory activity in various conditions, including herniation of the nucleus pulposus (HNP), by inhibiting tumour necrosis factor (TNF)-α, but the effects of long-term use are unknown. Here, we investigated the effect of dexamethasone (DEXA) on TNF-α-stimulated intervertebral disc cells by monitoring the expression and localization of NF-κB in the cytoplasm and nucleus. Cultured human intervertebral disc cells were left untreated or treated with only TNF-α, only DEXA, or with TNF-α and DEXA simultaneously. Cytoplasmic and nuclear proteins were extracted and Western blotted after 10 min, 1 or 2 h, to evaluate the expression of p50, p65, p52, and p100 (components of NF-κB). Immunofluorescence analysis was used to determine the subcellular localization of the proteins at 1 h. DEXA had limited effects on NF-κB expression in TNF-α-stimulated disc cells within the first 10 min. At 1 h, DEXA prevented the TNF-α-stimulated translocation of p50, p52, and p65. After 2 h, DEXA reduced the nuclear expression of p50, p65, and p52. Thus, DEXA resulted in delayed expression of NF-κB components and inhibited the translocation of p50, p52, and p65 to the nucleus, which would prevent expression of the corresponding genes. Therefore, following stimulation with TNF-α, transcriptional regulation of NF-κB in disc cells is mainly mediated via the classical pathway, but also to some extent via the alternative pathway. Hence, blockade of sub-acute inflammatory changes in HNP can be achieved by early injection of steroids, whereas long-term injection of a steroid may initiate NF-κB autophosphorylation.
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This work was supported by The Catholic University of Korea Daejeon St. Mary’s Hospital, and a clinical research institute grant funded by The Catholic University of Korea Daejeon St. Mary’s Hospital.
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Meiling Quan and Sang-Eun Park equally contributed to the first authorship.
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Quan, M., Park, SE., Lin, Z. et al. Steroid treatment can inhibit nuclear localization of members of the NF-κB pathway in human disc cells stimulated with TNF-α. Eur J Orthop Surg Traumatol 25 (Suppl 1), 43–51 (2015). https://doi.org/10.1007/s00590-014-1499-8
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DOI: https://doi.org/10.1007/s00590-014-1499-8