STAT-3-Aktivierung in humanen endometrialen Primärzellkulturen durch LIF und IL-11

Leukemia inhibitory factor (LIF) and Interleukin (IL) 11, two cytokines of the IL-6 Family, have been identified as regulatory molecules during blastocyst implantation in mice. IL-11 knock out (k.o.) mice, as well as LIF Rß k.o. mice demonstrated fertility problems. Thus the hypothesis was generated that IL-11 and LIF might be important for human fertility as well. IL-6 type cytokines use the JAK/STAT Pathway for signal transduction. To demonstrate that IL-11 and LIF influence human endometrial cells, we incubated different groups of endometrial cells either with IL-11 or LIF. Then non-activated and activated phosphorylated (p) STAT 3 was detected in these cells and in control-groups. To show the response of the human endometrium to these cytokines in different cell populations and different stages of the menstrual cycle epithelial cells, stromal cells and in vitro decidualised stromal cells were employed. No activation of STAT 3 was seen in human epithelial cells via IL-11, nor LIF, which was probably caused by the low cell count, a methodical problem. IL-11 was shown to activate STAT 3 mainly in in vitro decidualised cells. LIF seems to activate STAT 3 in stromal cells during the entire hormonally influenced parts of the menstrual cycle. But also for LIF the strongest activation was detected in in vitro decidualised cells. Our results demonstrate that signal transduction for these cytokines in human endometrial cells occurs via the JAK/STAT Pathway. The main target cells for these cytokines are the decidual cells, which play a significant role for implantation and therefore for fertility