Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 699-706 |
| Number of pages | 8 |
| Journal | Current Eye Research |
| Volume | 38 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2013 |
Bibliographical note
Funding Information:This work was supported by the Korea Science & Engineering Foundation (KOSEF) through the MRC for Cell Death Disease Research Center at the Catholic University of Korea. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
Keywords
- IL-6
- IL-8
- MTOR
- Orbital fibroblasts
- PDCD4
- Rapamycin
- TNF-α