Interleukin-1 system in the materno-trophoblast unit in human implantation: immunohistochemical evidence for autocrine/paracrine function.

Abstract

Interleukin-1 receptor type I, IL-1 beta, IL-1 receptor antagonist, and human macrophages were immunohistochemically localized in the villous trophoblast, maternal-trophoblast interphase, and maternal decidua during early human implantation. Immunostaining for IL-1 receptor type I was present in the syncytiotrophoblast and hyperplastic endometrial glands in the maternal decidua. Immunoreactive IL-1 beta was present in the villous cytotrophoblast, syncytiotrophoblast, intermediate trophoblast, and maternal stromal decidual cells. IL-1 receptor antagonist staining was observed in the glandular endometrium of the maternal decidua and in isolated cells located inside the chorionic villi, intervillous space, and maternal decidua. Mature human macrophages, as defined by both CD/68+ and HAM56+, were present in the chorionic villi, maternal blood of intervillous space, and maternal decidua. Co-localization studies demonstrated that macrophages in all of the reported locations also stained for immunoreactive IL-1 beta. Our results show the shared presence in maternal and embryonic tissues of this receptor-agonist-antagonist system during early human implantation. This finding supports an autocrine/paracrine role for the IL-1 system in human implantation.

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].…”

Role of Placental Cytokines in Transcriptional Modulation of HIV Type 1 in the Isolated Villous Trophoblast

“…granular lymphocytes, are a source of GM-CSF, IFN-a and -g, IL-1, IL-2, IL-6, IL-10, LIF, M-CSF, TGF-b, and TNF-a. 16,[32][33][34][35] The main purpose of this cytokine network is to maintain homeostasis between the semiallogeneic fetus and the mother and to support the growth and development of the placenta and the conceptus. The interplay between cytokines is complex, based on a multitude of positive and negative regulatory loops and hierarchically organized control mechanisms.…”

Human chorionic gonadotropin stimulates matrix metalloproteinases-2 and -9 in cytotrophoblastic cells and decreases tissue inhibitor of metalloproteinases-1, -2, and -3 in decidualized endometrial stromal cells

“…Cytokines expressed in the secretory endometrium, such as LIF , IL-6, or IGFBP-1, can modulate trophoblastic invasion (10)(11)(12). Interestingly, these regulators of trophoblastic MMPs have been shown to be influenced by the embryonic signal hCG (18,21,34).…”

“…In contrast to tumor invasion, trophoblastic invasion into the maternal endometrium is a highly coordinated and controlled process, requiring a subtle interaction between trophoblast and endometrium (9). Several cytokines such as leukemia inhibitory factor (LIF), interleukin (IL)-1b , IL-6, insulin-like growth factor binding protein (IGFBP)-1, and tumor necrosis factor (TNF)-a are potential regulators of trophoblastic invasion (10)(11)(12). The activity of MMPs is directly inhibited by specific tissue inhibitors of metalloproteinases (TIMPs) (13).…”