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High glucose solution and spent dialysate stimulate the synthesis of transforming growth factor-beta1 of human peritoneal mesothelial cells: effect of cytokine costimulation

Authors
 DH Kang  ;  YS Hong  ;  HJ Lim  ;  JH Choi  ;  DS Han  ;  KI Yoon 
Citation
 Peritoneal Dialysis International, Vol.19(3) : 221-230, 1999 
Journal Title
 Peritoneal Dialysis International 
ISSN
 0896-8608 
Issue Date
1999
MeSH
Blotting, Northern ; Blotting, Western ; Dialysis Solutions/pharmacology* ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/metabolism ; Glucose/pharmacology* ; Humans ; Interleukin-1/pharmacology* ; Peritoneal Dialysis* ; Peritoneum/cytology ; Peritoneum/metabolism* ; Peritonitis/metabolism ; Transforming Growth Factor beta/biosynthesis* ; Tumor Necrosis Factor-alpha/pharmacology*
Abstract
OBJECTIVE: To investigate the effect of high glucose and spent peritoneal dialysate on the transforming growth factor-beta1 (TGFbeta1) synthesis of cultured human peritoneal mesothelial cells (HPMCs) and to examine the effect of costimulation with high glucose or spent dialysate, and cytokines, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNFalpha) on TGFbeta1 synthesis of HPMCs. DESIGN: HPMCs were exposed to different concentrations of glucose (30, 60, and 90 mmol/L) or spent peritoneal dialysate for 48 hours in the absence or presence of IL-1beta (1 ng/mL) and TNFalpha(1 ng/mL).TGFbeta1 mRNA expression was assessed by Northern blot analysis and TGFbeta1 protein release by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). RESULTS: Exposure of HPMCs to high glucose conditions (30, 60, and 90 mmol/L of D-glucose) induced 2.3-, 3.6-, and 4.0-fold increases inTGFbeta1 mRNA expression of HPMC with enhancedTGFbeta1 protein synthesis and secretion into the media, whereas there were no significant changes in TGFbeta1 synthesis with equimolar concentrations of D-mannitol. Incubation with spent dialysate also significantly increased TGFbeta1 mRNA expression and protein secretion compared to control media (p < 0.05). Stimulation with IL-1beta (1 ng/mL) or TNFalpha (1 ng/mL) resulted in a significant increase in TGFbeta1 mRNA expression after 48 hours: 2.7 and 2.1 times the control level, respectively. However,TNFalpha-induced increase in TGFbeta1 mRNA expression was not translated intoTGFbeta1 protein secretion, while IL-1beta stimulation induced a significant increase in TGFbeta1 protein secretion as well as TGFbeta1 mRNA expression. Combined stimulation by high glucose or spent dialysate, together with IL-1beta or TNFalpha, showed a greater increase in TGFbeta1 mRNA expression and protein secretion compared to stimulation by high glucose or spent dialysate alone. CONCLUSION: Our results clearly show that high glucose solution and spent dialysate themselves might be sufficient to stimulate the production of TGFbeta1 by peritoneal mesothelial cells. In peritoneal dialysis patients, this state of chronic induction of TGFbeta1 is further exacerbated in the presence of peritonitis because of the stimulatory effect of proinflammatory cytokines, resulting in augmented TGFbeta1 synthesis, thus promoting peritoneal fibrosis.
Full Text
http://www.pdiconnect.com/content/19/3/221.abstract
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Han, Dae Suk(한대석)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173853
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