title: TNF-alpha decreases expression of somatostatin, somatostatin receptors, and cortistatin in human coronary endothelial cells.
abstract: BACKGROUND
  The objective of this study was to determine the expression of somatostatin (SST) and its receptors (SSTRs) and their regulation by TNF-alpha as well as cell proliferation in response to SST in human endothelial cells.
  
  
  METHODS
  Human coronary artery endothelial cells (HCAECs) were cultured without or with TNF-alpha (0.1, 1, or 10 ng/ml) for 24 h. The mRNA levels of SST, SSTR-1-5, as well as a housekeeping gene (beta-actin) were determined by real-time RT-PCR. Expression of SSTR-2 was also demonstrated by immunofluorescence staining. Cell proliferation in response to SST treatment (0.04, 0.2, or 1 ng/ml) was performed by [3H]thymidine incorporation.
  
  
  RESULTS
  Without TNF-alpha treatment, HCAECs showed mRNA expression of SST, SSTR-1, SSTR-2, and SSTR-5. The mRNA of SSTR-2 was expressed at a higher level than that of SSTR-1 and SSTR-5. However, SSTR-3 and SSTR-4 were not expressed or were minimally expressed. After treatment with TNF-alpha, the mRNA levels of SST, SSTR-1, SSTR-2, and SSTR-5 were significantly reduced in a dose-dependent fashion. TNF-alpha (1 ng/ml) reduced SST, SSTR-1, SSTR-2, and SSTR-5 by 93, 51, 85, and 99%, respectively, compared to controls (P < 0.001, t test). The immunoreactivity of SSTR-2 was also reduced after TNF-alpha treatment. SST-treated cells showed a significant reduction in [3H]thymidine incorporation in a dose-dependent manner. TNF-alpha treatment decreased SST inhibitory potential in cell proliferation.
  
  
  CONCLUSIONS
  HCAECs express SST, SSTR-1, SSTR-2, and SSTR-5, which are all decreased by TNF-alpha treatment. Furthermore, treatment with exogenous SST significantly reduces cell proliferation, and this inhibitory effect is also decreased by TNF-alpha.
authors.affiliation: Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Yan
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Chai
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Peter H
authors.initials: PH
authors.lastname: Lin
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yao
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D009479:Neuropeptides; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D014409:Tumor Necrosis Factor-alpha; C099323:cortistatin; C101130:somatostatin receptor type 1; D013004:Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2