Localization of interleukin-1 type I receptor and interleukin-1 beta in human endometrium throughout the menstrual cycle.

Abstract

Previous studies in the human suggest that the interleukin-1 (IL-1) system, may be an important paracrine/autocrine mediator in local intercellular interaction in endometrial tissue. In this study we have determined that IL-1 receptor type I (IL-1R tI) is expressed at the messenger RNA (mRNA) and protein levels in glandular cells and its ligand, IL-1 beta has been localized by immunohistochemical methods in endothelial cells and isolated stromal cells in the human endometrium throughout the menstrual cycle. IL-1R tI mRNA was detected in glandular epithelium using both specific complementary DNA and complementary RNA 32P-labeled probes. Human glandular epithelium contains a 5.1-kilobase mRNA transcript throughout the complete menstrual cycle. Quantitative densitometric analysis of slot blot hybridization signals shows an increase of IL-1R tI mRNA in both early and mid-late secretory phases in comparison with the proliferative phase (P < 0.05). IL-1R tI protein was localized in endometrial glandular epithelial cells using both indirect immunofluorescence and avidin-biotin-peroxidase methods. However, more intense staining for IL-1R tI was observed in lumenal epithelial cells compared with the staining present deep in the endometrial glands. Using the same methods, IL-1 beta was detected in endothelial cells of spiral vessels and isolated stromal cells throughout the menstrual cycle, and an increased staining from proliferative to secretory phase was observed. The detection of IL-1R tI in the human endometrial epithelium and its ligand, IL-1 beta, in isolated stromal cells and endothelial cells, is another example of possible communication between the immune and reproductive systems with special relevance to human implantation.

Human Endometrial Stromal Interleukin-1 Beta: Autocrine Secretion and Inhibition by Interleukin-1 Receptor Antagonist

“…Both IL-1α and IL-1β are produced in both human endometrial epithelial cells and ESCs [11, 12]. IL-1ra, however, is produced mainly in human endometrial epithelial cells rather in ESCs [16, 17, 18].…”

“…Both epithelial and stromal cells in human endometrium produce IL-1α/β constitutively throughout the menstrual cycle [11, 12]. This indicates that decidualization of human ESCs is always suppressed in vivo by endometrial IL-1.…”

Cytokines: Important for implantation?

“…This alternative explanation is not necessarily only a "pro domo" argument: It is indeed conceivable that absence of a cytokine during early embryonic life results in the expansion of a redundant alternative pathway, and that such a development cannot take place in adult life. Nevertheless, data from Simon suggest that IL-1 is important, though not critical [49][50][51][52][53].…”

The Transcription of Corticotropin-Releasing Hormone in Human Endometrial Cells Is Regulated by Cytokines

“…These two phenomena have a strong inflammatory component, and the associated cytokines participate as early regulators of the system. Indeed, endometrial cells produce interleukins IL-1, IL-6 and leukemia inhibitory factor (LIF), a pleiotropic cytokine of the IL-6 family, and express their receptors [12, 13, 14, 15]. There are several lines of evidence suggesting that these cytokines play important regulatory roles in implantation and decidualization.…”