title: AP-1 transcription factors, mucin-type molecules and MMPs regulate the IL-11 mediated invasiveness of JEG-3 and HTR-8/SVneo trophoblastic cells.
abstract: This study examines the IL-11 mediated activation of downstream signaling and expression of effector molecules to resolve the controversies associated with the IL-11 mediated regulation of the invasiveness of two commonly used trophoblastic cell models viz. JEG-3 and HTR-8/SVneo cells. It has been reported that IL-11 increases the invasiveness of JEG-3 cells while, reduces the invasiveness of HTR-8/SVneo cells. Invasion assay performed simultaneously for both the cell lines confirmed the above findings. In addition, HTR-8/SVneo cells showed a higher basal invasiveness than JEG-3 cells. Western blot showed the IL-11 mediated activation of STAT3(tyr705) and STAT1(tyr701) in both the cell lines. However, IL-11 activated the ERK1/2 phosphorylation in JEG-3 cells but, inhibited it in HTR-8/SVneo cells. Within 10 min of IL-11 treatment, p-STAT3(tyr705) was localized inside the nucleus of both the cell lines but, there was enhanced co-localization of protein inhibitor of activated STAT1/3 (PIAS1/3) and p-STAT3(tyr705) in HTR-8/SVneo cells and not in JEG-3 cells. This could be reason for the poor responsiveness of STAT3 responsive genes like mucin 1 (MUC1) in HTR-8/SVneo cells and not in JEG-3 cells. Further, microarray analysis of the IL-11 treated cells revealed differential responsiveness of JEG-3 as compared to HTR-8/SVneo cells. Several family of genes like activator protein-1 (AP-1) transcription factors (Jun and Fos), mucin-type molecules, MMP23B etc showed enhanced expression in IL-11 treated JEG-3 cells while, there was no response or decrease in their expression in IL-11 treated HTR-8/SVneo cells. Expression of these molecules was confirmed by quantitative RT-PCR. In addition, HTR-8/SVneo cells also showed a significant decrease in the expression of MMP2, MMP3 and MMP9 upon IL-11 treatment. Hence, IL-11 mediated differential activation of signaling and expression of effector molecules is responsible for the differential invasive response of JEG-3 and HTR-8/SVneo cells.
authors.affiliation: Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Suman
authors.forename: Geeta
authors.initials: G
authors.lastname: Godbole
authors.forename: Ravi
authors.initials: R
authors.lastname: Thakur
authors.forename: Diana M
authors.initials: DM
authors.lastname: Morales-Prieto
authors.forename: Deepak N
authors.initials: DN
authors.lastname: Modi
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Satish K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D017370:Interleukin-11 / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D016023:Integrins; D017370:Interleukin-11; D020782:Matrix Metalloproteinases; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D018396:Mucin-1; D009077:Mucins; D010750:Phosphoproteins; D050828:Protein Inhibitors of Activated STAT; D050796:STAT3 Transcription Factor; D019714:Tissue Inhibitor of Metalloproteinases; D018808:Transcription Factor AP-1; C117468:PDPN protein, human; D000098853:Podoplanin; C484745:PIAS3 protein, human