Rapamycin Enhances TNF-α-Induced Secretion of IL-6 and IL-8 through Suppressing PDCD4 Degradation in Orbital Fibroblasts

Purpose: To investigate the effects of rapamycin on the TNF-alpha-induced secretion of interleukin-6 (IL-6) and IL-8 in orbital fibroblasts and its possible mechanism. Materials and methods: Orbital fibroblasts were obtained from patients with thyroid-associated ophthalmopathy. IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. The down-regulation of PDCD4 was performed by PDCD4 siRNA transfection. Results: Rapamycin significantly enhanced TNF-alpha-induced IL-6 and IL-8 secretion from orbital fibroblasts. Down-regulation of PDCD4 by PDCD4 siRNA transfection reduced TNF-alpha-induced IL-6 and IL-8 secretion from orbital fibroblasts. In addition, TNF-alpha was found to promote the mTOR-dependent proteasome-mediated degradation of PDCD4. Rapamycin increased PDCD4 expression via the inhibition of TNF-alpha-induced PDCD4 degradation in orbital fibroblasts. Conclusion: Rapamycin enhances the TNF-alpha-induced secretion of IL-6 and IL-8 by suppressing PDCD4 degradation in orbital fibroblasts.