Problem: Macrophage migration inhibitory factor (MIF), a potent immuno-modulatory, angiogenic and tissue remodeling factor, is markedly expressed in ectopic endometrial implants and may play key role in the capability of this tissue to grow and develop into the host tissue. The objective of this study was to determine whether macrophage-derived cytokines, such as interleukin (IL)-1, which is overproduced by endometriosis women's peritoneal macrophages and found in elevated concentration in their peritoneal fluid, may play a role in MIF synthesis and secretion by ectopic endometrial cells.
Methods of study: Primary cultures of endometriotic cells exposed to IL-1beta and evaluation of MIF protein by immunocytofluorescence and ELISA, and mRNA by quantitative real-time PCR and nuclear transcription assays (run-on).
Results: Interleukin-1beta acts rapidly on endometriotic cells and stimulated MIF secretion and mRNA steady-state levels in a dose and time-dependent manner. IL-1beta treatment had no significant effect on MIF mRNA half-life and stability, but acted predominantly by up-regulating MIF gene transcription as assessed by run-on.
Conclusion: These data clearly indicate that IL-1 can be involved in the up-regulation of MIF expression by ectopic endometrial implants. Such an interaction between IL-1 and MIF may have an important impact on endometriotic cell growth and endometriosis pathophysiology.