Capellino, S. and Montagna, P. and Villaggio, B. and Soldano, S. and Straub, R. H. and Cutolo, M. (2008) Hydroxylated estrogen metabolites influence the proliferation of cultured human monocytes: possible role in synovial tissue hyperplasia. CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 26 (5). pp. 903-909. ISSN 0392-856X,
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Introduction 17 beta-estradiol, estrone, and several of their hydroxylated metabolites, have been found to be significantly increased ill synovial fluid of rheumatoid arthritis (RA) patients. In this study, we investigated whether the estrogen metabolites are able to exert direct effects on monocyte cell proliferation, which is important in RA synovial tissue activation and growth. Methods Human monocytes (THP-1) were treated with the following estrogen metabolites at different concentrations (front 10-M-8, 10(-9)M, 10(-10)M to 10(-11)M) for 24, 48 and 72 hours: 16-hydroxyestrone (160H-E1), 16-hydroxyestradiol (160H-E2), 4-hydroxyestrone (40H-E1), 4-hydroxyestradiol (40H-E2), 2-hydroxyestrone (20H-E1) and 2-hydroxyestradiol (20H-E2). Monocytes were activated with interfiron-gamma (INF-gamma). Cell cultures were also performed in presence of tamoxifen (10(-7)M) to evaluate whether the estrogen metabolites act through the estrogen receptors (ER). Cell growth was detected by MTT test and cell viability through the LDH release assay. Results 40H-E1 and 20H-E1 significantly increased cell growth at low concentration (10(-10)M), whereas they significantly reduced cell proliferation at high concentrations (10-9M). 160H-E2 and 40H-E2 induced opposite effects: cell proliferation at high concentration and antiproliferative action at low doses. On the contrary, 160H-E1 and 20H-E2 were found to be estrogen metabolites that induced cell proliferative effects for most of the tested doses. Tamoxifen caused the loss of effects on cell proliftrationfor almost all the metabolites. Conclusions This study first demonstrates that different downstream estrogen metabolites interfere with monocyte proliferation and generally might modulate the immune response. Therefore, since estrogen metabolite/ratios are altered in the synovial fluid of RA patients, they might play important roles at least in RA synovial tissue hyperplasia.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS; BREAST CANCER-CELLS; RHEUMATOID-ARTHRITIS; IN-VITRO; ESTRADIOL; FLUID; 2-HYDROXYESTRONE; MACROPHAGES; RECEPTORS; ANDROGEN; Hydroxy-estrogen metabolites; estrogens; monocytes; synovitis; synovial tissue hyperplasia; rheumatoid arthritis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 08:14 |
| Last Modified: | 26 Oct 2020 08:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30326 |
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