Modulation of cell growth and apoptosis by sex hormones in cultured monocytic THP-1 cells.
Several authors have reported the regulation of apoptotic phenomena by sex hormones in different cell lines, including T lymphocytes and mononuclear cells. Since androgens can modulate the programmed cell death in responsive cell lines, we decided to investigate the induction of apoptosis in THP-1 cells following their differentiation into macrophage-like cells and exposure to sex hormones. In addition, we decided to evaluate the proto-oncogene Bax and Fas (CD 95) and cleaved PARP (poly-adp-ribose-polymerase) expression in the same cultured cells. The results showed for the first time the dose-/time-dependent regulation of the apoptotic event in human monocytic THP-1 cells treated with different concentrations of androgens. No significant changes were observed for estrogen-treated and unstimulated control cells. In particular, the cells, after stimulation with androgens but not with estrogens, were found to be positive for the proto-oncogene Bax, Fas, and for cleaved subunits of PARP expression as demonstrated with different assays including immunocytochemical assay and Western blot analysis. In conclusion, these results support the possibility of sex hormone modulation of apoptosis in macrophage-like cells, with interesting therapeutic perspectives in rheumatoid arthritis.
Laboratory and Division of Rheumatology, Department of Internal Medicine and Medical Specialities, University of Genova, Genova, Italy. mcutolo@unige.it
Maurizio
M
Cutolo
Alberto
A
Sulli
Chiara
C
Craviotto
Lamberto
L
Felli
Carmen
C
Pizzorni
Bruno
B
Seriolo
Barbara
B
Villaggio
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000473:pathology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
C494826:BAX protein, human; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D013739:Testosterone; D004958:Estradiol; D011065:Poly(ADP-ribose) Polymerases