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Cytokines decrease glutaminase expression in human fibroblasts

P Sarantos¹, A Abouhamze, S Abcouwer

¹Department of Surgery, University of Florida College of Medicine, Gainesville.

|August 1, 1994

Summary

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Pro-inflammatory cytokines, such as IL-1 and TNF-alpha, reduce glutaminase expression in fibroblasts, potentially impairing wound healing by limiting essential metabolic intermediates.

Area of Science:

Cell biology
Biochemistry
Molecular biology

Background:

Fibroblast glutamine metabolism is crucial for wound healing processes like energy production and cell growth.
Cytokines are known to inhibit fibroblast proliferation, suggesting a potential impact on their metabolic pathways.

Purpose of the Study:

To investigate the effect of pro-inflammatory cytokines on glutamine metabolism in fibroblasts.
To examine the influence of cytokines on the expression of glutaminase, a key enzyme in intracellular glutamine metabolism.

Main Methods:

Human foreskin fibroblasts were treated with various pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, IFN-gamma) at different concentrations.
Glutaminase activity, protein levels (Western blotting), and mRNA levels (Northern blotting, nuclear run-ons) were measured.

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Main Results:

Cytokines significantly decreased glutaminase activity, protein, and mRNA levels after 12 hours of incubation.
The reduction in glutaminase expression was dose-independent and indicated transcriptional regulation.

Conclusions:

Pro-inflammatory cytokines inhibit glutaminase expression in cultured human fibroblasts.
This inhibition of glutamine metabolism may limit crucial intermediates, potentially impairing fibroblast proliferation and wound healing.