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Nuclear factor kappa B (NFκB) is a family of transcription factors involved in signalling between IL1 and TNFα receptors and cytokines and adhesion molecules in a number of cell types, including those of the human endometrium. In this study, we used immunocytochemistry to investigate the in vivo expression of the p50, IκBα and IκBβ NFκB components in endometrium obtained from normal fertile women throughout the menstrual cycle. All three components were expressed by both the stromal and epithelial cells of the endometrium and staining was predominately seen in the cytoplasm of the cells. Staining for p50 was more intense in the epithelial compartment than the stromal compartment. Staining in the stromal compartment was low to moderate throughout the cycle but, in the epithelial compartment, staining was cycle dependent and increased slightly during the mid-secretory phase. The staining patterns for IκBα and IκBβ were similar. As for p50, staining for both proteins was greater in the epithelial compartment compared to the stromal compartment and stromal cell staining was low to moderate throughout the cycle. However, in contrast to p50, staining for the IκB proteins in epithelial cells decreased during the mid-secretory phase of the cycle. Although the immunocytochemistry technique used is only semi-quantitative, the results suggest an increased expression of the active and a decreased expression of the inhibitory NFκB components by the endometrium at the time of implantation. If confirmed, it would suggest that NFκB is involved in the control of factors important in the implantation process. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The production of tumour necrosis factor a (TNF-α) by cultured human endometrial epithelial and stromal cells prepared from endometrium obtained at different stages in the menstrual cycle has been investigated. TNF-α was not detectable in the supernatants of stromal cell cultures prepared from endometrial tissue obtained at any time in the menstrual cycle. TNF-α production by endometrial epithelial cells in culture varied depending on the time in the cycle at which the endometrial tissue was taken. Cells prepared from tissue obtained during the late proliferative phase of the cycle produced more TNF-α than those prepared from tissue obtained at other times in the cycle. In addition, a small increase in TNF-α production was seen by cells prepared from tissue obtained during the mid-secretory phase of the cycle. Interieukin 1 (IL-1) (1.4–140 pmol/1) caused a dose-dependent increase in TNF-α production by cells prepared from both proliferative and secretory endometrium. Maximum LL-1-stimulated increases in TNF-α production were similar in cells from both proUferative and secretory endometrium and typically reached from four to 10 times basal values. High doses of progesterone, either alone or in the presence of oestradiol, also affected TNF-a production by epithelial cells. TNF-α production by cells prepared from proliferative endometrium was increased by progesterone. In contrast, TNF-α production by cells prepared from secretory endometrium was decreased in the presence of progesterone. The effects of steroids on TNF-α production were less marked than that of IL-1, with values increasing or decreasing to a maximum of three times the basal value. Placental protein 14 (PP14) (0.18 and 1.8 nmol/1) also increased TNF-α production by cells prepared from proliferative tissue, but had no effect on its production by cells prepared from secretory endometrium. PP14-stimulated TNF-α levels typically only reached a maximum of two times basal values. [ABSTRACT FROM PUBLISHER]