Evidence for the expression of interleukin (IL)-18, IL-18 receptor and IL-18 binding protein in the human endometrium.
To see whether the interleukin (IL)-18 system is operative in the endometrium, we examined the expression of IL-18, IL-18 receptor (IL-18R) and IL-18 binding protein (IL-18BP), the substance known to neutralize IL-18 activity, in this tissue. Reverse transcription-polymerase chain reaction analyses showed that IL-18, IL-18R and IL-18BP mRNA were constitutively expressed without significant fluctuation throughout the menstrual cycle. When epithelial cells and stromal cells were cultured separately, the expression levels of IL-18 mRNA in epithelial cells were about 18-fold higher compared to those in stromal cells. Furthermore, the IL-18 precursor protein was detected by Western blot analysis in cultured epithelial cells but not in stromal cells. Recombinant human IL-18 stimulated the secretion of interferon (IFN)-gamma by resident bone marrow-derived cells in the endometrium. On the other hand, IFN-gamma up-regulated the IL-18BP expression both in cultured epithelial cells and stromal cells. Thus, we have presented evidence for the presence of the IL-18 system in the human endometrium. In light of its immunomodulatory roles in a variety of tissues, this system may afford protection against pathogenic micro-organisms and provide a regulatory mechanism for controlled trophoblast invasion by modulating a local cytokine network.
Yoshino
O
O
Department of Obstetrics and Gynecology, University of Tokyo, Tokyo 113-8655, Japan.
Osuga
Y
Y
Koga
K
K
Tsutsumi
O
O
Yano
T
T
Fujii
T
T
Kugu
K
K
Momoeda
M
M
Fujiwara
T
T
Tomita
K
K
Taketani
Y
Y
D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins / Q000494:pharmacology
D006023:Glycoproteins; C508572:IL18R1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins; C118370:interleukin-18 binding protein; D007371:Interferon-gamma