PARENT SESSION
Uterus/Oviduct

INTERLEUKIN-1 AND hCG INDUCE PROSTAGLANDIN PRODUCTION IN CULTURED HUMAN ENDOMETRIAL CELLS.

Kang, Jihong¹, Parent, Julie¹, Akoum, Ali¹, Fortier, Michel¹, ¹

ABSTRACT- Human uterine endometrium is an active site of cytokine and hormone actions. Interleukin-1 (IL-1) is one cytokine responsive to infection and involved in implantation. Human chorionic gonadotropin (hCG) is the embryonic signal in the human, and it can be detected in the blood or urine of a pregnant woman soon after implantation. Both of them may play an important role in the regulation of prostaglandins (PGs). In this study, we investigated the effect of IL-1 and hCG on PGE₂ and PGF₂ production in human endometrial stromal and epithelial cells in culture. The cells were cultured from biopsies for a few days. After reaching confluence, they were incubated in the presence of IL-1 (0, 0.01, 0.1 and 1ng/ml) or hCG (0, 0.01, 0.1 and 1g/ml) for 24h. In both stromal and epithelial cells, basal PGE₂ release was greater than PGF₂. In stromal cells, IL-1 resulted in a dose-dependent increase in PGE₂ and PGF₂ secretion. A similar induction of PGF₂, but not PGE₂ , was seen in epithelial cells. In both cell types, a significant increase of prostaglandins was observed at 1ng/ml of IL-1. However, the increase of prostaglandin production induced by IL-1 (1ng/ml) was much greater in stromal cells than in epithelial cells. The ratio of PGE₂/PGF₂ decreased with increasing concentration of IL-1 in both stromal and epithelial cells. Western blot analysis showed that IL-1 induced an increase in cyclooxygenase-2 (COX-2) protein level only in stromal cells. No change was observed in cyclooxygenase-1 (COX-1) protein level in either cell type. PGE₂ production was up-regulated by hCG in a dose-dependent manner in stromal cells and the stimulation was stronger in late luteal phase than in proliferative phase. In epithelial cells, hCG did not appreciably up-regulate PGE₂ or PGF₂ production. No detectable change of COX-1 or COX-2 protein levels was found in either cell type, as measured by Western blot. In summary, these results suggest that IL-1 probably up-regulated PGE₂ and PGF₂ production by increasing COX-2 expression in stromal cells. In both stromal and epithelial cells, PGF₂ secretion was more significantly induced by IL-1. HumanCG was inclined to increase PGE₂ secretion in stromal cells, which is consistent with its luteotrophic function. It is inferred that the stromal cell of human endometrium is a preferred target for both IL-1 and hCG action in the human endometrium.

KEY WORDS: IL-1, hCG, prostaglandins , human endometrial cells