Expression of interleukin (IL)-11 receptor by the human endometrium in vivo and effects of IL-11, IL-6 and LIF on the production of MMP and cytokines by human endometrial cells in vitro.
Interleukin (IL)-6, leukaemia inhibitory factor (LIF) and IL-11 belong to the same family of cytokines whose receptors utilize gp130 as the signalling molecule. We have investigated the expression of the IL-11 receptor, IL-11Ralpha, protein in the human endometrium in vivo and the effects of IL-6, LIF and IL-11 on the production of metalloproteinases (MMPs) and cytokines by cultured endometrial epithelial and stromal cells. Immunostaining showed that IL-11Ralpha was expressed in both epithelial and stromal cells, with epithelial staining being more intense than stromal staining and little variation in staining in either compartment throughout the cycle. Incubation of both stromal and epithelial cells with IL-6, LIF and IL-11 had no effect on MMP-2, -7, -9, transforming growth factor (TGF)beta or IL-1beta production or cell growth. IL-6 and LIF also had no effect on tumour necrosis factor (TNF)alpha production, but IL-11 caused a dose-dependent decrease in TNFalpha production by epithelial cells. IL-6 receptor, LIF receptor and gp130 were all expressed by cultured stromal and epithelial cells, showing that the lack of effect is not due to lack of expression of the receptor components. The results show that although IL-6, LIF and IL-11 signal through the same molecule, they may have different effects in endometrial cells, suggesting the activation of different signalling pathways, which may ultimately be important in the control of endometrial function.
Division of Biomedical Sciences/BMRC, Sheffield Hallam University, City Campus, Sheffield, UK.
B A
BA
Cork
E M
EM
Tuckerman
T C
TC
Li
S M
SM
Laird
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D017370:Interleukin-11 / Q000378:metabolism* / Q000494:pharmacology; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism* / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D053606:Receptors, OSM-LIF; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D006131:Growth Inhibitors; C508428:IL11RA protein, human; C494199:IL6ST protein, human; D007375:Interleukin-1; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D050822:Cytokine Receptor gp130; D020782:Matrix Metalloproteinases