Uterine epithelial cell secretion of interleukin-1 alpha induces prostaglandin E2 (PGE2) and PGF2 alpha secretion by uterine stromal cells in vitro.

Abstract

Uterine epithelial cells (UEC) were isolated from cycling mice and cultured on Matrigel-coated nitrocellulose filters to determine their ability to secrete interleukin-1 alpha (IL-1 alpha) in response to ovarian steroids and induce prostaglandin (PG) secretion by uterine stromal cells (USC). UEC cultured in a polarized manner secreted IL-1 alpha with an 8- to 10-fold apical vs. basal preference, as determined by an enzyme-linked immunosorbent assay. There was no effect of 17 beta-estradiol, progesterone, or 17 beta-estradiol plus progesterone on IL-1 alpha secretion by UEC. The mean total IL-1 alpha secreted to the apical and basal secretory compartments over the 24-h incubation period was 0.8 +/- 0.16 and 0.07 +/- 0.05 ng/2 x 10(5) cells, respectively. Cytokine bioactivity, as determined by [3H]thymidine incorporation into D10 cells in response to UEC-conditioned medium, paralleled the pattern of IL-1 alpha secretion observed using the immunoassay. In addition to the in vitro secretion of IL-1 alpha by polarized UEC, pooled uterine fluid collected from proestrous stage mice contained IL-1 alpha at a concentration of 0.7 ng/ml, indicating that IL-1 alpha is released into the uterine lumen in vivo. Coculture with UEC or treatment with conditioned medium from either the apical or basal UEC secretory compartments induced a several-fold increase in the secretion of PGE2 and PGF2 alpha by USC. Relative to untreated USC, PGE2 was induced to a greater extent than PGF2 alpha. The addition of polyclonal anti-IL-1 alpha significantly inhibited the ability of UEC-conditioned medium and UEC coculture to induce PG secretion by USC. In addition, mouse recombinant IL-1 alpha added at a concentration similar to that secreted by UEC stimulated USC PGE2 and PGF2 alpha secretion in a manner similar to that observed with UEC coculture. Experiments designed to determine the cell type specificity of the induction of PG secretion by USC indicated that conditioned medium from a human UEC line (RL95), a rat prostate epithelial cell line (E4), and a mouse fibroblast cell line (10T1/2) induced PG secretion to an extent that paralleled their ability to induce D10 cell proliferation. The present results demonstrate the ability of UEC to secrete IL-1 alpha in a vectorial manner. Soluble products secreted by UEC are capable of stimulating PGE2 and PGF2 alpha secretion by USC, and IL-1 alpha appears to be a significant factor contributing to this effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Interleukin 1 Signaling Is Regulated by Leukemia Inhibitory Factor (LIF) and Is Aberrant in Lif−/− Mouse Uterus1

“…Intense staining of IL1A was observed in the decidua on D5 and D6 but markedly reduced in Lif-null uteri from D4 onwards. Since these animals lack decidualization and IL1 is known to induce decidualizing molecules [30,31], the lack of IL1A here is consistent with it being a mediator of LIF-induced decidualization. In vitro studies in murine endometrial stromal cells have also shown that the extracellular matrix glycoprotein tenascin C (TNC) expression is up-regulated by Il1a [7,59].…”

“…Epithelial derived IL1A has been previously reported to upregulate the synthesis of PTGES2 and PGF 2a in mouse and rat uterine stromal cells [30,31], and other studies in vitro have shown that IL1A increases levels of mRNA for Ptgs2 (a rat-limiting enzyme for PG synthesis) in rat uterine stromal cells [32]. Evidence from in vivo studies has demonstrated that mRNA and protein levels of PTGS2 are reduced in the uterine stroma of Lif-deficient mice at the implantation site [7,33].…”

Intrauterine oxytocin system

“…For example, thyroid epithelial cells secrete thyroid hormone as well as thyroglobulin apically, whereas another secretory product, thrombospondin, is secreted via the basolateral compartment (Prabakaran et al 1993). Uterine epithelial cells secrete many biologically active compounds in a polarized fashion: interleukin-6, interleukin-1α, complement component C3, and the secretory glycoprotein USP-1 are all secreted apically (Julian et al 1992;Jacobs and Carson 1993), whereas PGF2α is secreted basolaterally in both mouse and bovine uterine epithelial cells (Asselin et al 1996). This latter finding is compatible with the idea that, following stimulation by OT at the apical site, basolaterally secreted PGF2α interacts with the myometrium to elicit myometrial contractions.…”

Expression of Toll-Like Receptors (TLR) and Responsiveness to TLR Agonists by Polarized Mouse Uterine Epithelial Cells in Culture1

“…Central to this protection are the uterine epithelial cells, which provide a physical barrier and produce a spectrum of antimicrobials, including complement, lysozyme, lactoferrin, defensins, and secretory leukocyte protease inhibitor [1,2]. Studies have demonstrated that epithelial cells from the mouse and rat uterus could be grown on cell inserts; following growth to confluence, these cells form tight junctions and preferentially secrete cytokines in a polarized fashion [3][4][5][6]. Epithelial cells also secrete an array of chemokines and cytokines, which are crucial for the recruitment and activation of innate immune cells [7,8].…”