Involvement of MAPK pathway in TNF-alpha-induced MMP-9 expression in human trophoblastic cells.
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-kappaB (NF-kappaB) 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-kappaB 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-kappaB activation and (b) SAPK/JNK pathway that activates AP-1.
Cohen
Marie
M
Department of Obstetrics and Gynaecology, Maternity, Hormone Laboratory, University of Geneva, Boulevard de la Cluse, Switzerland.
Meisser
Arielle
A
Haenggeli
Luise
L
Bischof
Paul
P
D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9