Expression of nuclear factor κ B in human endometrium; role in the control of interleukin 6 and leukaemia inhibitory factor production

Abstract

Expression of the rel-A component of nuclear factor κ B (NFκB) by human endometrial cells was investigated by immunocytochemical analysis of cryostat sections cut from endometrial biopsy material and of cultured endometrial epithelial cells. In-vivo expression of rel-A was low in epithelial cells in endometrium obtained during the proliferative phase of the cycle, but increased in these cells during the secretory phase and was maximal at the time of implantation. In-vivo expression of rel-A by stromal cells did not vary greatly throughout the cycle, but showed a slight peak at the time of ovulation. In contrast similar expression of rel-A was seen in short-term cultures of epithelial cells prepared from both proliferative and secretory endometrium. Addition of the NFκB inhibitor SN50 (5 μg/ml) to confluent cultures of endometrial epithelial cells inhibited interleukin (IL)-1α (10 ng/ml) and tumour necrosis factor α (TNFα) (10 ng/ml) stimulated IL-6 (P < 0.001 and P< 0.01 respectively) and LIF (P< 0.01 and P< 0.05 respectively) production. The proteasome inhibitor MG132 (0.3 and 3 μmol/l) also caused a dose-dependent decrease in IL-1α and TNFα-stimulated IL-6 (P< 0.001 and P < 0.001 respectively) and leukaemia inhibitory factor (LIF) (P < 0.001 and P < 0.001 respectively) production by endometrial epithelial cells. The results support the hypothesis that NFκB mediates signalling between IL-1 and TNFα receptors and the expression of LIF and IL- 6 in endometrial epithelial cells.