{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T23:28:59Z","timestamp":1792970939541,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-166092"],"award-info":[{"award-number":["PJT-166092"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["G21-0031494"],"award-info":[{"award-number":["G21-0031494"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["PJT-166092"],"award-info":[{"award-number":["PJT-166092"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["G21-0031494"],"award-info":[{"award-number":["G21-0031494"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HSFC Ontario Mid-Career Investigator Award","award":["PJT-166092"],"award-info":[{"award-number":["PJT-166092"]}]},{"name":"HSFC Ontario Mid-Career Investigator Award","award":["G21-0031494"],"award-info":[{"award-number":["G21-0031494"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sex differences in the development and progression of cardiovascular disease are well established, but the effects of sex hormones on macrophage polarization and pro-atherogenic functions are not well described. We hypothesize that sex hormones directly modulate macrophage polarization, and thereby regulate the progression of atherosclerosis. Bone marrow-derived monocytes from adult male and female C57BL\/6 mice were differentiated into macrophages using macrophage colony-stimulating factor (20 ng\/mL) and pre-treated with either 17\u03b2-estradiol (100 nM), testosterone (100 nM), or a vehicle control for 24 h. Macrophages were polarized into pro- or anti-inflammatory phenotypes and the effects of sex hormone supplementation on the gene expression of macrophage phenotypic markers were assessed using RT-qPCR. Inflammatory markers, including IL-1\u03b2, were quantified using an addressable laser bead immunoassay. A transwell migration assay was used to determine changes in macrophage migration. Sex differences were observed in macrophage polarization, inflammatory responses, and migration. Pre-treatment with 17\u03b2-estradiol significantly impaired the gene expression of inflammatory markers and the production of IL-1\u03b2 in inflammatory macrophages. In anti-inflammatory macrophages, 17\u03b2-estradiol significantly upregulated the expression of anti-inflammatory markers and enhanced migration. Pre-treatment with testosterone enhanced anti-inflammatory mRNA expression and impaired the production of IL-1\u03b2. Our observations suggest a protective role of 17\u03b2-estradiol in atherogenesis that may contribute to the sexual dimorphisms in cardiovascular disease observed in human patients.<\/jats:p>","DOI":"10.3390\/ijms25020951","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T07:47:16Z","timestamp":1705045636000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Investigating the Effects of Sex Hormones on Macrophage Polarization"],"prefix":"10.3390","volume":"25","author":[{"given":"Sophie","family":"Enright","sequence":"first","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute, 237 Barton Street E, Hamilton, ON L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7843-885X","authenticated-orcid":false,"given":"Geoff H.","family":"Werstuck","sequence":"additional","affiliation":[{"name":"Thrombosis and Atherosclerosis Research Institute, 237 Barton Street E, Hamilton, ON L8L 2X2, Canada"},{"name":"Department of Medicine, McMaster University, 1280 Main St. W, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e015634","DOI":"10.1161\/JAHA.119.015634","article-title":"State of the Science in Women\u2019s Cardiovascular Disease: A Canadian Perspective on the Influence of Sex and Gender","volume":"9","author":"Norris","year":"2020","journal-title":"J. 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