Induction of TGF-β1 synthesis in D-glucose primed human proximal tubular cells by IL-1β and TNFα
1996
Induction of TGF-β1 synthesis in D-glucose primed human proximal tubular cells by IL-1β and TNFα. The aim of the present study was to examine whether the induction of TGF- β 1 synthesis by the pro-inflammatory macrophage derived cytokines, IL-1 β or TNF α , was modified by alterations in D-glucose concentrations. Stimulation of growth arrested HPTC with IL-1 β or TNF α resulted in increased expression of TGF- β 1 mRNA. The transcript was demonstrable 60 minutes after the addition of IL-1 β , and apparent steady-state mRNA levels were achieved after six hours. Following stimulation with TNF α , TGF- β 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 β or TNF α (both at 1 ng/ml), there was no difference in the absolute amount of TGF- β 1 mRNA induced by these two stimuli (14.8 ± 5.6 vs. 19.7 ± 4.9 pm). Despite induction of TGF- β 1 mRNA following stimulation with IL-1 β or TNF α , neither stimulus increased TGF- β 1 protein synthesis or release. Pre-exposure of HPTC to 25mm D-glucose for 48 hours and subsequent stimulation with IL-1 β resulted in the secretion of latent TGF- β 1 in both a time and dose dependent manner. This effect was not apparent following TNF α stimulation of D-glucose primed HPTC. Stimulation of TGF- β 1 synthesis by IL-1 β in D-glucose primed cells was inhibited by cycloheximide but not by actinomycin-D. Examination of D-glucose induced TGF- β 1 mRNA revealed that IL-1 β , but not TNF α , increased the stability of the D-glucose induced transcript. These results demonstrate that the interaction of D-glucose and IL-1 β lead to secretion of TGF- β 1 by HPTC. In contrast, such an interaction was not demonstrable between D-glucose and TNF α . This may be explained by the ability of IL-1 β to stabilize D-glucose-induced TGF- β 1 mRNA.
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