Tumour necrosis factor-alpha up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-kappaB.
BACKGROUND
A series of controlled changes including proliferation, secretion and menstrual shedding occur in the human endometrium during every normal menstrual cycle. Macrophage migration inhibitory factor (MIF), a multifunctional cytokine with numerous proinflammatory, immunomodulatory and angiogenic properties, appears to be expressed in the human endometrium and to follow a regulated cycle phase-dependent expression, but the mechanisms underlying endometrial MIF expression remain to be fully elucidated.


RESULTS
Results from enzyme-linked immunosorbent assay (ELISA) demonstrated a significant dose- and time-dependent increase in MIF secretion by human endometrial cells in response to tumour necrosis factor-alpha (TNF-alpha) (0.1-100 ng/ml). This increase was also observed at the mRNA level as shown by reverse transcription (RT)-PCR. Curcumin (10(-8) mol/l), a known nuclear factor (NF)-kappaB inhibitor, inhibited the TNF-alpha-induced pIkappaB phosphorylation as shown by western blotting, NF-kappaB translocation into the nucleus as shown by electrophoretic mobility shift assay, and MIF synthesis and secretion as measured by ELISA and RT-PCR. The expression of a dominant-negative NF-kappaB inhibitor (IkappaB) significantly decreased the TNF-alpha-induced MIF promoter activity as analysed by transient cell transfection.


CONCLUSIONS
These results indicate clearly that TNF-alpha up-regulates the expression of MIF in endometrial stromal cells. This took place possibly through NF-kappaB activation, and may play an important role in the physiology of the human endometrium.
Cao
W G
WG
Unité d'endocrinologie de la reproduction, Centre de Recherche, Hôpital Saint-François d'Assise, Centre Hospitalier Universitaire de Québec, Faculté de Médecine, Université Laval, Québec, Canada.
Morin
M
M
Sengers
V
V
Metz
C
C
Roger
T
T
Maheux
R
R
Akoum
A
A
D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation
D008263:Macrophage Migration-Inhibitory Factors; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha