THE ROLE OF CYTOKINES IN HUMAN ENDOMETRIUM - THE INHIBITORY EFFECT OFIL-1 AND TNF-ALPHA ON IN-VITRO DECIDUALIZATION AND MESSENGER-RNA EXPRESSION OF M-CSF, SCF AND LIF IN THE HUMAN ENDOMETRIUM

With a culture system of human endometrial stromal cells, the effects of cytokines of interleukin (IL)-1, tumor necrosis factor (TNF)alpha, interferon (IFN)beta, and IFN gamma were examined. In a dose-dependent manner, IL-1 and TNF alpha inhibited progesterone-induced in vitro de cidualization indicated by PRL production and cellular transformation with no cytotoxicity. IFN beta had no effect, but IFN gamma inhibited PRL production caused by cytotoxicity. By Northern blot analysis and q uantitative reverse transcription-polymerase chain reaction, human end ometrium was shown to express the genes of macrophage colony-stimulati ng factor (M-CSF), stem cell factor (SCF) and leukemia inhibitory fact or (LIF). During stromal cell culture with progesterone, mRNA expressi on 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 e xpression of SCF mRNA between proliferative and secretory phase endome trium, but higher expression of SCF mRNA was observed in decidua of ea rly pregnancy. LIF mRNA was more strongly expressed in secretory phase endometria than in proliferative ones. In culture experiments, SCF ge ne expression was higher in stromal cells, on the other hand, LIF mRNA was more strongly expressed in glandular epithelial cells. But no sig nificant changes in SCF or LIF mRNAs were identified in our culture sy stem for in vitro decidualization. These findings suggested an importa nt regulatory role of cytokines in endometrial differentiation, and, i n addition, endometrial stromal cells and glandular cells may play ind ependent 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.