Human endometrial leukemia inhibitory factor and interleukin-6: control of secretion by transforming growth factor-beta-related members.
OBJECTIVE
The implantation process is closely linked to the fundamental question of the tolerance of the maternal immune system. The main objective of this study was to investigate whether different members of the transforming growth factor-beta (TGF-beta) superfamily could intervene in the first steps of embryo implantation by modulating the secretion of proimplantatory leukemia inhibitory factor (LIF) and in the tolerance of the fetal graft by regulating proinflammatory interleukin (IL)-6 secretion by human endometrial epithelium (EEC) in vitro.


METHODS
EEC were isolated from biopsies collected from 16 informed and consenting fertile women and were cultured for 72 h. Cytokine measurements (LIF and IL-6) were realized by ELISA.


RESULTS
TGF-beta(1) (from 10(-12) to 10(-8)M), -beta(2), -beta(3) and activin A (10(-10) and 10(-8)M) increased LIF secretion by EEC cultures. Inhibin B (10(-10) and 10(-8)M) did not stimulate LIF production by human EEC. Contrastingly, TGF-beta(1) (from 10(-12) to 10(-8)M), -beta(2), -beta(3) and activin A (10(-10) and 10(-8)M) reduced IL-6 release by the same cells. Activin A at 10(-8) M also significantly reduced the stimulating effect of IL-1beta (10(-9)M) which is known to stimulate LIF production by EEC. Only the highest concentration of inhibin B (10(-8)M) reduced IL-6 secretion by EEC, but did not modulate IL-1beta-induced stimulation of IL-6 secretion.


CONCLUSIONS
Besides their role in the control of the process of implantation and in the induction of embryonic mesoderm, different members of the TGF-beta superfamily may also contribute in the reproductive process by enhancing endometrial proimplantatory LIF secretion and reducing proinflammatory IL-6 release by EEC.
Perrier d'Hauterive
Sophie
S
University of Liège, Department of Medicine, Center of Immunology, Institute of Pathology CHU-B23, Liège-Sart Tilman, Belgium. sperrier@ulg.ac.be
Charlet-Renard
Chantal
C
Dubois
Michel
M
Berndt
Sarah
S
Goffin
Frederic
F
Foidart
Jean-Michel
JM
Geenen
Vincent
V
D028341:Activins / Q000276:immunology / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects / Q000276:immunology*; D004717:Endometrium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D028322:Inhibin-beta Subunits / Q000276:immunology / Q000494:pharmacology; D007265:Inhibins / Q000276:immunology / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D008875:Middle Aged; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3
D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; C422405:activin A; C044147:activin B; C422364:inhibin B; D028341:Activins; D007265:Inhibins; D028322:Inhibin-beta Subunits