Effect of tumour necrosis factor-α in combination with interferon-γ on first trimester extravillous trophoblast invasion
| Autor: | Barbara A. Innes, Judith N. Bulmer, Roger F. Searle, Therese Hannon, Katsuhiko Naruse, Stephen C. Robson, HA Otun, Gendie E. Lash |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Proteases
medicine.medical_specialty Immunology Blotting Western Fluorescent Antibody Technique Gene Expression Apoptosis Matrix metalloproteinase Biology Endometrium Interferon-gamma Pregnancy Internal medicine Plasminogen Activator Inhibitor 1 medicine Immunology and Allergy Humans Receptors Tumor Necrosis Factor Type II Secretion Receptor Cytotrophoblast Tumor Necrosis Factor-alpha Serine Endopeptidases Obstetrics and Gynecology Trophoblast Urokinase-Type Plasminogen Activator Trophoblasts Killer Cells Natural Pregnancy Trimester First medicine.anatomical_structure Endocrinology Reproductive Medicine Receptors Tumor Necrosis Factor Type I embryonic structures Cancer research Female Plasminogen activator |
| Zdroj: | Journal of reproductive immunology. 88(1) |
| ISSN: | 1872-7603 |
| Popis: | Successful pregnancy is dependent upon invasion of the uterine tissues by extravillous trophoblast cells (EVT). The mechanisms that control trophoblast invasion are unclear, but several cytokines and growth factors appear to be involved. We have previously demonstrated that IFN-γ inhibits EVT invasion via a mechanism partially dependent on an increase in EVT apoptosis and decreased secretion of matrix metalloproteinase (MMP)-2. In the current study we show that TNF-α, both alone and in combination with IFN-γ, inhibits EVT invasion via a mechanism associated with increased trophoblast apoptosis, decreased trophoblast proliferation and/or altered production of active proteases. TNF-α and its receptors, TNF-αRI and TNF-αRII, were immunolocalised in the placental bed. Uterine natural killer (uNK) cells, EVT and villous cytotrophoblast were shown to all produce TNF-α, and TNF-α receptors were primarily immunolocalised to EVT in the placental bed. TNF-α increased EVT apoptosis, decreased villous cytotrophoblast proliferation and increased expression of pro-MMP-9 (but not active MMP-9), urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI)-1 by EVT. The combination of TNF-α and IFN-γ inhibited EVT via a mechanism associated with increased EVT apoptosis, reduced proliferation, reduced pro-MMP-2 secretion and increased secretion of uPA. TNF-α is one of several decidua-derived factors with the capacity to inhibit EVT invasion. The mode of activity of TNF-α was modified by the presence of IFN-γ, suggesting that the local cytokine milieu may be critical in determining spatial and/or temporal changes in EVT invasion. |
| Databáze: | OpenAIRE |
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