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

• Published in: Current eye research Vol. 38; no. 6; pp. 699 - 706
• Main Authors: Lee, Won-Mo, Paik, Ji-Sun, Cho, Won-Kyung, Oh, Eun-Hye, Lee, Seong-Beom, Yang, Suk-Woo
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare USA, Inc 01.06.2013; Taylor & Francis
• Subjects: Adipose Tissue - cytology; Adult; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Female; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Graves Ophthalmopathy - drug therapy; Graves Ophthalmopathy - metabolism; Graves Ophthalmopathy - pathology; Humans; IL-6; IL-8; Immunosuppressive Agents - pharmacology; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Male; mTOR; Orbit - cytology; orbital fibroblasts; PDCD4; Rapamycin; RNA, Small Interfering - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sirolimus - pharmacology; TNF-α; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0271-3683; 1460-2202
• DOI: 10.3109/02713683.2012.750368

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.