title: Rapamycin enhances TNF-α-induced secretion of IL-6 and IL-8 through suppressing PDCD4 degradation in orbital fibroblasts.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Rapamycin enhances the TNF-α-induced secretion of IL-6 and IL-8 by suppressing PDCD4 degradation in orbital fibroblasts.
authors.affiliation: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Won-Mo
authors.initials: WM
authors.lastname: Lee
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Paik
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Oh
authors.forename: Seong-Beom
authors.initials: SB
authors.lastname: Lee
authors.forename: Suk-Woo
authors.initials: SW
authors.lastname: Yang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049970:Graves Ophthalmopathy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D009915:Orbit / Q000166:cytology; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D016209:Interleukin-8; C114487:PDCD4 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D020123:Sirolimus