Interleukin 1beta 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-alpha) synthesis is increased in the uterus of diabetic rats and that the epithelial layer lining the uterine lumen is the major site of TNF-alpha over-production. In the present study, TNF-alpha secretion was found to be stimulated 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-epithelial cells may mediate the influence of high D-glucose on TNF-alpha production by uterine epithelial cells. Immunocytochemical analysis revealed the reproducible presence of a small proportion of macrophages in primary cultures. Macrophages of the RAW 264.7 cell line were found to secrete more interleukin (IL)-1beta (but not TNF-alpha) when cultured in high D-glucose. TNF-alpha production in WEG-1 cells was increased upon exposure to IL-1beta 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 cells do not produce IL-1beta, the data lend support to the hypothesis that uterine epithelial cells synthesize high levels of TNF-alpha in response to hyperglycaemia via an increase in IL-1beta secretion by stromal macrophages.
Pampfer
S
S
OBST 5330 Research Unit, University of Louvain Medical School, Brussels, Belgium. pampfer@obst.ucl.ac.be
Cordi
S
S
Dutrieux
C
C
Vanderheyden
I
I
Marchand
C
C
De Hertogh
R
R
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*; D014599:Uterus / Q000166:cytology* / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose