title: Upregulation of Bcl-2 at the foetal-maternal interface from mice undergoing abortion.
abstract: Several burning questions remain unanswered in pregnancy-related research. Pro- and anti-inflammatory cytokines orchestrate an intriguing interaction leading either to the development of a normal individual or to its rejection. Augmented Th1 cytokines' production is involved in immunological rejection of the foetus. Excessive production of Th1 cytokines, particularly of tumour necrosis factor (TNF)-alpha, also triggers apoptosis. Thus, in the present work we investigated the incidence of apoptosis in a well-known experimental model of Th1-induced abortion, characterized by increased local TNF-alpha levels. Apoptosis of lymphocytes as well as their Th1 and Th2 cytokine production were analysed by flow cytometry. TNF-alpha mRNA levels were additionally analysed by real time reverse transcription-polymerase chain reaction (RT-PCR) in placental and decidual samples. Total placental apoptosis activity was investigated by measuring caspase-3 activity and by TdT-mediated dUTP nick end label staining. Immunohistochemistry, Western blot and real time RT-PCR were used to localize and quantify several anti- and pro-apoptotic molecules at the foetal-maternal interface. Despite elevated Th1 levels at the foetal-maternal interface, mice undergoing abortion presented comparable apoptotic rates. Interestingly, we found a significant upregulation of the anti-apoptotic Bcl-2 protein at the foetal-maternal interface from abortion-prone mice, while no changes could be observed for pro-apoptotic molecules. In the light of our results, we conclude that there is no evidence of increased apoptosis in mice undergoing immunological abortion in spite of elevated TNF-alpha levels. This is probably due to a selective upregulation of anti-apoptotic pathways (i.e. Bcl-2) at the foetal-maternal interface as a compensatory and/or protective mechanism.
authors.affiliation: Institute of Medical Immunology, Charite, Campus Virchow Klinikum, Medical University of Berlin, Berlin, Germany.
authors.forename: A Zambon
authors.initials: AZ
authors.lastname: Bertoja
authors.forename: M L
authors.initials: ML
authors.lastname: Zenclussen
authors.forename: I
authors.initials: I
authors.lastname: Wollenberg
authors.forename: S
authors.initials: S
authors.lastname: Paeschke
authors.forename: A
authors.initials: A
authors.lastname: Sollwedel
authors.forename: K
authors.initials: K
authors.lastname: Gerlof
authors.forename: C
authors.initials: C
authors.lastname: Woiciechowsky
authors.forename: H-D
authors.initials: HD
authors.lastname: Volk
authors.forename: A C
authors.initials: AC
authors.lastname: Zenclussen
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D003656:Decidua / Q000276:immunology / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha