Induction of TGF-beta 1 synthesis in D-glucose primed human proximal tubular cells by IL-1 beta and TNF alpha

  • Phillips A
  • Topley N
  • Steadman R
 et al. 
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The aim of the present study was to examine whether the induction of TGF-beta 1 synthesis by the pro-inflammatory macrophage derived cytokines, IL-1 beta or TNF alpha, was modified by alterations in D-glucose concentrations. Stimulation of growth arrested HPTC with IL-1 beta or TNF alpha resulted in increased expression of TGF-beta 1 mRNA. The transcript was demonstrable 60 minutes after the addition of IL-1 beta, and apparent steady-state mRNA levels were achieved after six hours. Following stimulation with TNF alpha, TGF-beta 1 mRNA was detectable after 15 minutes and reached steady state levels by two hours. Quantitative RT-PCR revealed that following six hours stimulation with either IL-1 beta or TNF alpha (both at 1 ng/ml), there was no difference in the absolute amount of TGF-beta 1 mRNA induced by these two stimuli (14.8 +/- 5.6 vs. 19.7 +/- 4.9 PM). Despite induction of TGF-beta 1 mRNA following stimulation with IL-1 beta or TNF alpha, neither stimulus increased TGF-beta 1 protein synthesis or release. Pre-exposure of HPTC to 25 mM D-glucose for 48 hours and subsequent stimulation with IL-1 beta resulted in the secretion of latent TGF-beta 1 in both a time and dose dependent manner. This effect was not apparent following TNF alpha stimulation of D-glucose primed HPTC. Stimulation of TGF-beta 1 synthesis by IL-1 beta in D-glucose primed cells was inhibited by cycloheximide but not by actinomycin-D. Examination of D-glucose induced TGF-beta 1 mRNA revealed that IL-1 beta, but not TNF alpha, increased the stability of the D-glucose induced transcript. These results demonstrate that the interaction of D-glucose and IL-1 beta lead to secretion of TGF-beta 1 by HPTC. In contrast, such an interaction was not demonstrable between D-glucose and TNF alpha. This may be explained by the ability of IL-1 beta to stabilize D-glucose-induced TGF-beta 1 mRNA.

Author-supplied keywords

  • Cells, Cultured
  • Cycloheximide/pharmacology
  • Dactinomycin/pharmacology
  • Glucose/*pharmacology
  • Humans
  • Interleukin-1/*pharmacology
  • Kidney Tubules, Proximal/cytology/drug effects/*me
  • Polymerase Chain Reaction
  • Protein Synthesis Inhibitors/pharmacology
  • RNA, Messenger/biosynthesis/isolation & purificati
  • Stimulation, Chemical
  • Transforming Growth Factor beta/*biosynthesis
  • Tumor Necrosis Factor-alpha/*pharmacology

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  • A O Phillips

  • N Topley

  • R Steadman

  • K Morrisey

  • J D Williams

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