title: Interleukin 1 beta is induced by interleukin 11 during decidualization of human endometrial stromal cells, but is not released in a bioactive form.
abstract: Blastocyst implantation is dependent on the differentiation of endometrial stromal cells (ESC) into decidual cells. Decidualization of human ESC in vitro is enhanced by interleukin 11 (IL11), with associated changes in gene expression. Genes downstream of IL11 may provide targets for the treatment of implantation failure or the development of non-hormonal contraceptives. This study aimed to examine the effect of IL11 on interleukin 1 beta (IL1B) mRNA and protein expression during in vitro decidualization of ESC. Cells were decidualized with 17beta-estradiol and medroxyprogesterone acetate in the presence or absence of exogenous IL11, and IL1B mRNA was quantified by real-time RT-PCR. Inactive proIL1B and bioactive IL1B in cell lysates and conditioned media were measured using specific immunoassays. Secretion of bioactive IL1B from decidualizing ESC was investigated by in vitro stimulation of decidualizing cells with lipopolysaccharide, interferon gamma or human chorionic gonadotropin. Immunohistochemistry was carried out on cycling and pregnant decidua using an antibody specific for bioactive IL1B. Exogenous IL11 increased by 28-fold the abundance of IL1B mRNA in decidualizing ESC, and total immunoreactive IL1B was also increased. However, this was not reflected in bioactive IL1B secretion from these cells, and none of the tested stimuli were able to induce its release. Bioactive IL1B was detected in vivo at very low levels and at discrete foci in late secretory phase and first trimester decidua. This regulation of latent and bioactive IL1B at the fetal-maternal interface may prime decidual cells to respond rapidly to immunological challenge or to signals from the blastocyst during implantation.
authors.affiliation: Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton, Vic. 3168, Australia. christine.white@princehenrys.org
authors.forename: Christine A
authors.initials: CA
authors.lastname: White
authors.forename: Evdokia
authors.initials: E
authors.lastname: Dimitriadis
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Sharkey
authors.forename: Chelsea J
authors.initials: CJ
authors.lastname: Stoikos
authors.forename: Lois A
authors.initials: LA
authors.lastname: Salamonsen
mesh_terms: D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010064:Embryo Implantation / Q000276:immunology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D017370:Interleukin-11 / Q000378:metabolism / Q000494:pharmacology; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D006063:Chorionic Gonadotropin; D017370:Interleukin-11; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma