The Role of Cytokines in Human Endometrium: The Inhibitory Effect of IL-1 and TNF α on <I>in Vitro</I> Decidualization and mRNA Expression of M-CSF, SCF and LIF in the Human Endometrium

Abstract

With a culture system of human endometrial stromal cells, the effects of cytokines of interleukin (IL)-1, tumor necrosis factor (TNF)α, interferon (IFN)β, and IFNγ were examined. In a dose-dependent manner, IL-1 and TNFα inhibited progesterone-induced in vitro decidualization indicated by PRL production and cellular transformation with no cytotoxicity. IFNβ had no effect, but IFNγ inhibited PRL production caused by cytotoxicity. By Northern blot analysis and quantitative reverse transcription-polymerase chain reaction, human endometrium was shown to express the genes of macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF) and leukemia inhibitory factor (LIF). During stromal cell culture with progesterone, mRNA expression of both M-CSF and its receptor, c-fms, was significantly increased in a dose- and time-dependent manner. There was no difference in the expression of SCF mRNA between proliferative and secretory phase endometrium, but higher expression of SCF mRNA was observed in decidua of early pregnancy. LIF mRNA was more strongly expressed in secretory phase endometria than in proliferative ones. In culture experiments, SCF gene expression was higher in stromal cells, on the other hand, LIF mRNA was more strongly expressed in glandular epithelial cells. But no significant changes in SCF or LIF mRNAs were identified in our culture system for in vitro decidualization. These findings suggested an important regulatory role of cytokines in endometrial differentiation, and, in addition, endometrial stromal cells and glandular cells may play independent roles in producing cytokines essential for local immune cell proliferation and/or differentiation. Thus an immune-endocrine network exists in the human uterus to regulate the endometrial function.