Submission Number: BRE-4-35-1

Abstract Number: 392

EFFECT OF CYTOKINES ON TISSUE INHIBITOR OF METALLOPROTEINASE (TIMP) MESSENGER RIBONUCLEIC ACID (MRNA) LEVELS IN CULTURED MOUSE ENDOMETRIAL STROMAL CELLS.

Brent M Bany* and Gilbert A Schultz*

Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada. ¹

Abstract:
TIMPs constitute a family of four genes (TIMPs 1-4) that specifically inhibit matrix metalloproteinases. TIMP expression in the mouse endometrium is believed to play a role in implantation and decidualization. However, little is known about how TIMP expression is controlled in the endometrium. The aim of the present study was to determine the effects of transforming growth factor beta-1 (TGFbeta-1), leukemia inhibitory factor (LIF), epidermal growth factor (EGF) and interleukin-1alpha (IL-1alpha) on TIMP mRNA levels in mouse endometrial stromal cells isolated from uteri sensitized for the decidual cell reaction. After isolation and plating, the cells were serum-starved for 24 h then treated with or without cytokine for 6 h. TIMP mRNA levels in the cells was determined by Northern blot analysis. TIMPs 1-3, but not TIMP-4, could be detected in the cells. TGFbeta-1 (5 ng/ml) caused a significant (P < 0.05) increase in steady-state TIMP-1 and -3 mRNA levels but had no effect on TIMP-2 mRNA levels. LIF (5 ng/ml) and IL-1alpha (20 ng/ml) had no effect on TIMP mRNA levels. While having no effect on TIMP-1 and -3 mRNA levels, EGF (40 ng/ml) caused a significant (P < 0.05) decrease in steady-state TIMP-2 mRNA levels. These results show that TGFbeta-1 and EGF can affect steady-state mRNA levels in mouse endometrial stromal cells isolated from uteri sensitized for the decidual cell reaction. Since their receptors are present in the endometrium, these cytokines might platy a role in modulating TIMP expression in the endometrium during implantation and decidualization. (This work was supported by Medical Research Council of Canada Grant, a Lalor Foundation Fellowship and a Alberta Heritage Foundation Fellowship) .

Keywords: Uterus, Endometrium, Cytokines, TIMPs

This abstract is being presented at: 8:00 AM in session:
Uterus/Oviduct I