Effect of recombinant human TNF-binding protein-1 and GnRH antagonist on mRNA expression of inflammatory cytokines and adhesion and growth factors in endometrium and endometriosis tissues in baboons.
OBJECTIVE
To evaluate the mechanism of action of recombinant human tumor necrosis factor (TNF)-binding protein-1 by assessing differential expression of messenger RNA (mRNA) for cytokines, matrix metalloproteinases, and growth and adhesion factors in baboons.


METHODS
Analysis of gene expression in a prospective randomized study.


METHODS
University Fertility Center.


METHODS
In the in vivo study, 14 baboons were randomly and subcutaneously (SC) treated with either phosphate-buffered saline (PBS), GnRH antagonist, or recombinant human TNF-binding protein-1 at the time of induction. In the ex vivo study, 4 baboons were treated by menstrual endometrium that had been incubated randomly with either PBS or recombinant human TNF-binding protein-1 before intrapelvic injection.


METHODS
In the in vivo study, analysis of 11 endometrial and 10 endometriosis biopsies included either PBS (n = 5), GnRH antagonist (n = 8), or recombinant human TNF-binding protein-1 (n = 8). In the ex vivo study, 2 endometrial and 4 endometriosis biopsies were analyzed from 4 baboons.


METHODS
The mRNA expression of TNF-alpha, IL-8, IL-6, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, intercellular adhesion molecule-1, matrix metalloproteinase-1, and regulated on activation, normal T-cell expressed and secreted were investigated using real-time reverse transcriptase-polymer chain reaction (PCR).


RESULTS
TGF-beta mRNA expression was decreased in endometriotic lesions from baboons treated with recombinant human TNF-binding protein-1 when compared with the placebo group.


CONCLUSIONS
Except TGF-beta, mRNA expression of inflammatory cytokines and adhesion/growth factors is not affected in endometrial and endometriosis biopsies from baboons after induction of endometriosis combined with either systemic injection of recombinant human TNF-binding or GnRH antagonist or ex vivo treatment with recombinant human TNF-binding protein-1. Further studies are needed to elucidate the mode of action on how inhibition of TNF-alpha activity prevents the development of endometriosis.
Kyama
Cleophas M
CM
Leuven University Fertility Centre, Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium.
Overbergh
Lutgart
L
Mihalyi
Attila
A
Cuneo
Silvio
S
Chai
Daniel
D
Debrock
Sophie
S
Mwenda
Jason M
JM
Mathieu
Chantal
C
Nugent
Noreen P
NP
D'Hooghe
Thomas M
TM
D000818:Animals; D001706:Biopsy; D002352:Carrier Proteins / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010215:Papio / Q000235:genetics*; D010919:Placebos; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010919:Placebos; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix