Jauquline Nordqvist1, Angelina Bernardi2, Ulrika Islander2, Hans Carlsten2. 1. Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: jauquline.nordqvist@rheuma.gu.se. 2. Department of Rheumatology and Inflammation Research, Centre for Bone and Arthritis Research (CBAR), Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Abstract
BACKGROUND/ OBJECTIVE: 17β-estradiol (E2) has major effects on the immune system. It induces thymic atrophy, inhibits both T and B lymphopoiesis and stimulates antibody production treatment with E2 has protective effects on the skeleton but is associated with negative side effects in reproductive organs. A tissue-selective estrogen complex (TSEC) comprise of estrogens combined with a selective estrogen receptor modulator (SERM). TSEC therapy displays the bone-protective effects of estrogen, while the negative side effects on reproductive organs are blocked by the SERM. In a recent publication we showed that treatment with the TSEC E2+bazedoxifene (bza) potently inhibits experimental arthritis and associated osteoporosis. In order to elucidate immunological mechanisms involved in those effects, the aim of this study was to investigate how E2+bza treatment affects the healthy immune system. METHODS: Ovariectomized C57BL/6N mice were treated with vehicle, E2, bza or E2+bza. Weights of uterus and thymus were determined and fluorescence-activated cell sorting was used to analyze B cell populations in bone marrow and spleen. Immunoglobulin production from B cells in bone marrow and spleen were determined using ELISPOT. RESULTS: Addition of bza to E2-treatment totally antagonized the E2-mediated proliferative effect on uterus. On the contrary, addition of bza to E2-treatment did not block the E2-induced thymic atrophy or inhibition of B lymphopoiesis, and did not block the E2-induced increase in immunoglobulin secretion from bone marrow B cells. CONCLUSIONS: Addition of bza to E2-treatment blocks E2-induced uteroproliferation but does not alter E2-mediated effects on thymus, B lymphopoiesis or B cell function.
BACKGROUND/ OBJECTIVE: 17β-estradiol (E2) has major effects on the immune system. It induces thymic atrophy, inhibits both T and B lymphopoiesis and stimulates antibody production treatment with E2 has protective effects on the skeleton but is associated with negative side effects in reproductive organs. A tissue-selective estrogen complex (TSEC) comprise of estrogens combined with a selective estrogen receptor modulator (SERM). TSEC therapy displays the bone-protective effects of estrogen, while the negative side effects on reproductive organs are blocked by the SERM. In a recent publication we showed that treatment with the TSEC E2+bazedoxifene (bza) potently inhibits experimental arthritis and associated osteoporosis. In order to elucidate immunological mechanisms involved in those effects, the aim of this study was to investigate how E2+bza treatment affects the healthy immune system. METHODS: Ovariectomized C57BL/6N mice were treated with vehicle, E2, bza or E2+bza. Weights of uterus and thymus were determined and fluorescence-activated cell sorting was used to analyze B cell populations in bone marrow and spleen. Immunoglobulin production from B cells in bone marrow and spleen were determined using ELISPOT. RESULTS: Addition of bza to E2-treatment totally antagonized the E2-mediated proliferative effect on uterus. On the contrary, addition of bza to E2-treatment did not block the E2-induced thymic atrophy or inhibition of B lymphopoiesis, and did not block the E2-induced increase in immunoglobulin secretion from bone marrow B cells. CONCLUSIONS: Addition of bza to E2-treatment blocks E2-induced uteroproliferation but does not alter E2-mediated effects on thymus, B lymphopoiesis or B cell function.
Authors: Pathum Thilakasiri; Jennifer Huynh; Ashleigh R Poh; Chin Wee Tan; Tracy L Nero; Kelly Tran; Adam C Parslow; Shoukat Afshar-Sterle; David Baloyan; Natalie J Hannan; Michael Buchert; Andrew Mark Scott; Michael Dw Griffin; Frederic Hollande; Michael W Parker; Tracy L Putoczki; Matthias Ernst; Ashwini L Chand Journal: EMBO Mol Med Date: 2019-04 Impact factor: 12.137