PURPOSE: To investigate the effects of rapamycin on the TNF-α-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-α-induced IL-6 and IL-8 secretion from orbital fibroblasts. Down-regulation of PDCD4 by PDCD4 siRNA transfection reduced TNF-α-induced IL-6 and IL-8 secretion from orbital fibroblasts. In addition, TNF-α was found to promote the mTOR-dependent proteasome-mediated degradation of PDCD4. Rapamycin increased PDCD4 expression via the inhibition of TNF-α-induced PDCD4 degradation in orbital fibroblasts. CONCLUSION: Rapamycin enhances the TNF-α-induced secretion of IL-6 and IL-8 by suppressing PDCD4 degradation in orbital fibroblasts.
PURPOSE: To investigate the effects of rapamycin on the TNF-α-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-α-induced IL-6 and IL-8 secretion from orbital fibroblasts. Down-regulation of PDCD4 by PDCD4 siRNA transfection reduced TNF-α-induced IL-6 and IL-8 secretion from orbital fibroblasts. In addition, TNF-α was found to promote the mTOR-dependent proteasome-mediated degradation of PDCD4. Rapamycin increased PDCD4 expression via the inhibition of TNF-α-induced PDCD4 degradation in orbital fibroblasts. CONCLUSION: Rapamycin enhances the TNF-α-induced secretion of IL-6 and IL-8 by suppressing PDCD4 degradation in orbital fibroblasts.
Authors: Zoe E Gillespie; Kimberly MacKay; Michelle Sander; Brett Trost; Wojciech Dawicki; Aruna Wickramarathna; John Gordon; Mark Eramian; Ian R Kill; Joanna M Bridger; Anthony Kusalik; Jennifer A Mitchell; Christopher H Eskiw Journal: Nucleus Date: 2015 Impact factor: 4.197
Authors: Sita Virakul; Poorichaya Somparn; Trairak Pisitkun; Peter J van der Spek; Virgil A S H Dalm; Dion Paridaens; P Martin van Hagen; Nattiya Hirankarn; Tanapat Palaga; Willem A Dik Journal: Front Endocrinol (Lausanne) Date: 2021-02-15 Impact factor: 5.555