Interleukin 1 beta mediates the effect of high D-glucose on the secretion of TNF-alpha by mouse uterine epithelial cells

Previous observations have shown that tumour necrosis factor alpha (TNF-alp ha) synthesis is increased in the uterus of diabetic rats and that the epit helial layer lining the uterine lumen is the major site of TNF-alpha over-p roduction. In the present study, TNF-alpha secretion,vas found to be stimul ated by high D-glucose levels in primary cultures of mouse uterine luminal cells but not in cultures of the mouse uterine epithelial WEG-1 cell line. Experiments were performed to investigate the possibility that non-epitheli al cells may mediate the influence of high D-glucose on TNF-alpha productio n by uterine epithelial cells. Immunocytochemical analysis revealed the rep roducible presence of a small proportion of macrophages in primary cultures . Macrophages of the RAW 264.7 cell line were found to secrete more interle ukin (IL)-1 beta (but not TNF-alpha) when cultured in high D-glucose, TNF-a lpha production in WEG-1 cells was increased upon exposure to IL-1 beta and both protein kinase-C and tyrosine kinase pathways appeared to be involved in TNF-alpha stimulation. Addition of IL-1 receptor antagonist to primary cultures partially abrogated the effect of high D-glucose, Since WEG-1 cell s do not produce IL-1 beta, the data lend support to the hypothesis that ut erine epithelial cells synthesize high levels of TNF-alpha in response to h yperglycaemia via an increase in IL-1 beta secretion by stromal macrophages , (C) 1999 Academic Press.