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Mol. Hum. Reprod. Advance Access originally published online on March 6, 2006
Molecular Human Reproduction 2006 12(4):225-232; doi:10.1093/molehr/gal023
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Involvement of MAPK pathway in TNF-{alpha}-induced MMP-9 expression in human trophoblastic cells

Marie Cohen, Arielle Meisser, Luise Haenggeli and Paul Bischof1

Department of Obstetrics and Gynaecology, Maternity, Hormone Laboratory, University of Geneva, Boulevard de la Cluse, Geneva, Switzerland

1 To whom correspondence should be addressed at: Laboratoire d’Hormonologie, 32 bd de la Cluse, 1211 Genève 14, Switzerland. E-mail: paul.bischof{at}hcuge.ch

The aim of this article was to investigate the signalling pathways involved in metalloproteinase-9 (MMP-9) expression induced by tumour necrosis factor-{alpha} (TNF-{alpha}) in first-trimester trophoblastic cells. TNF-{alpha}-induced MMP-9 expression, secretion and activity were completely blocked by stress-activated protein kinase/jun kinase (SAPK/JNK) and Erk inhibitors (SP600 125 and U0126 respectively) but not by p38 mitogen-activated protein kinase (MAPK) inhibitors (SB203 580 and SB202 190). Stimulation of HIPEC 65 cells with TNF-{alpha} caused phosphorylation of JNK and extracellular signal-regulated kinase 1/2 (Erk1/2), with a peak after 20 min of treatment. Transcription factors nuclear factor-{kappa}B (NF-{kappa}B) and activator protein 1 (AP-1)-binding site were identified as the cis-elements involved in TNF-{alpha} activation as determined by electromobility shift assays. TNF-{alpha}-induced transactivation of NF-{kappa}B was inhibited by U0126, whereas TNF-{alpha}-induced transactivation of AP-1 was inhibited by SP600 125. Taken together, these results indicate that in trophoblastic cells, TNF-{alpha} probably activates two different pathways leading to MMP-9 expression: (a) Erk1/2 pathway which in turn initiates NF-{kappa}B activation and (b) SAPK/JNK pathway that activates AP-1.

Key words: AP-1/cytotrophoblastic cells/Erk1/2/JNK/MMP-9/NF-{kappa}B/TNF-{alpha}


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