title: Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis.
abstract: In endometriosis, regurgitating endometrial cells fail to undergo apoptosis and implant themselves outside the uterus, particularly in the peritoneum. We studied Fas and FasL behaviour by evaluating the percentages of mFas and mFasL-bearing mononuclear cells from peritoneal fluid, the level of Fas and FasL gene expression at both mRNA and protein levels in the same cells, and the sFas and sFasL values in peritoneal fluid of 80 endometriotic women, at four stages of disease severity. We found no variation in percentage of mFas-bearing mononuclear cells; high and unchanging levels of Fas mRNA and protein, and high and invariable sFas values. Overproduction of sFas antagonises mFas function and plays a role as a decoy in the peritoneal fluid. The mFasL-bearing mononuclear cells and protein levels decreased from the minimal to the severe stage of disease. In contrast to FasL protein, FasL mRNA was overexpressed throughout the course of the disease. sFasL values were high and increased as the disease worsened. Our results showed a non-linear ratio between FasL mRNA and FasL protein levels. Abnormally elevated FasL mRNA may be due to dysregulation in several mechanisms controlling mRNA turnover. The high level of sFasL would be expected to down-regulate FasL activity and compete with the membrane form for mFas binding. As a consequence, mFas-bearing mononuclear cells may be unable to kill and in turn, may themselves become targets for killing by FasL-expressing endometriotic cells.
authors: Department of Gynecological Sciences, School of Medicine, Policlinico Universitario G. Martino, Via C. Valeria -Gazzi-, University of Messina, 98125 Messina, Italy. esturlese@unime.it
authors: Emanuele
authors: E
authors: Sturlese
authors: Francesca Maria
authors: FM
authors: Salmeri
authors: Giovanni
authors: G
authors: Retto
authors: Alfonsa
authors: A
authors: Pizzo
authors: Rosanna
authors: R
authors: De Dominici
authors: Francesca Venera
authors: FV
authors: Ardita
authors: Irene
authors: I
authors: Borrielli
authors: Norma
authors: N
authors: Licata
authors: Antonio Simone
authors: AS
authors: Laganà
authors: Vincenza
authors: V
authors: Sofo
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D001202:Ascitic Fluid / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D004715:Endometriosis / Q000276:immunology*; D004717:Endometrium / Q000473:pathology; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor