title: STAT3 enhances intracellular Fas-mediated apoptotic signals in HHUA human endometrial epithelial cells.
abstract: Several endometrial signal transducer and activator of transcription 3 (STAT3)-activating cytokines are reported to be essential for blastocyst implantation, with inhibition of STAT3 activation in the endometrium also reported to prevent implantation. To investigate STAT3 signals in endometrial epithelial cells, the activation and inactivation effects of STAT3 signals were examined in the human endometrial epithelial cell line HHUA, which is thought to retain many of the intracellular signaling pathways found in normal human endometrial epithelial cells. Five STAT3-activating cytokines, IL-11, IL-10, LIF, oncostatin M and leptin, enhanced the Fas-mediated apoptosis of the HHUA cells without any increase in cell surface Fas antigen expression. STAT3 siRNA transfection suppressed STAT3 expression in HHUA cells and significantly inhibited Fas-mediated cell death. These results indicate that intracellular apoptotic signals in HHUA cells are constitutively activated and regulated by STAT3-mediated signals. This apoptosis-promoting effect of STAT3 in HHUA cells is completely different from many previous reports demonstrating anti-apoptotic effects by STAT3 activation. The STAT3 signals in HHUA cells may be specific to the human endometrial epithelial cell lineage in the regulation of blastocyst implantation.
authors.affiliation: Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan. obgywmu@wakayama-med.ac.jp
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukumoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yukawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D016207:Cytokines; C491901:FAS protein, human; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D019014:fas Receptor