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Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression

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Abstract

The aim of this study was to examine the influence of sex on age-related changes in phenotype and functional capacity of rat macrophages. The potential role of estradiol as a contributing factor to a sex difference in macrophage function with age was also examined. Thioglycollate-elicited peritoneal macrophages derived from the young (2 months old) and the naturally senescent intact middle-aged (16 months old) male and female rats were tested for cytokine secretion and antimicrobial activity (NO and H2O2 production and myeloperoxidase activity). Serum concentration of estradiol and the expression of estrogen receptor (ER)α and ERβ on freshly isolated peritoneal macrophages were also examined. Decreased secretion of IL-1β and IL-6 by macrophages from middle-aged compared to the young females was accompanied with the lesser density of macrophage ERα expression and the lower systemic level of estradiol, whereas the opposite was true for middle-aged male rats. Macrophages in the middle-aged females, even with the diminished circulating estradiol levels, produce increased amount of IL-6, and comparable amounts of IL-1β, TNF-α, and NO to that measured in macrophages from the middle-aged males. Age-related changes in macrophage phenotype and the antimicrobial activity were independent of macrophage ERα/ERβ expression and estradiol level in both male and female rats. Although our study suggests that the sex difference in the level of circulating estradiol may to some extent contribute to sex difference in macrophage function of middle-aged rats, it also points to more complex hormonal regulation of peritoneal macrophage activity in females.

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Acknowledgements

This study is supported by the Ministry of Education, Science and Technological Development Republic of Serbia, Grant No 175050. The Ministry of Education, Science and Technological Development had no role in the study design, collection, analysis and interpretation of data, writing of the report, and decision to submit the article for publication. Authors express their gratitude to Tatjana Miletić, PhD (Health & Environment Department, Molecular Diagnostics, AIT Austrian Institute of Technology GmbH), for critical reading and valuable comments.

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Authors and Affiliations

  1. Immunology Research Centre “Branislav Janković”, Institute of Virology, Vaccines and Sera “Torlak”, Vojvode Stepe 458, Belgrade, 11221, Serbia

    Ivana Ćuruvija, Stanislava Stanojević, Veljko Blagojević & Biljana Vidić-Danković

  2. Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

    Nevena Arsenović-Ranin

  3. Department of Immunology, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia

    Mirjana Dimitrijević

  4. Department of Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Vesna Vujić

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  1. Ivana Ćuruvija
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Correspondence to Stanislava Stanojević.

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The experimental protocol and all procedures with animals and their care were approved by Ministry of Agriculture and Environmental Protection (license number 323-07-01577/2016-05/14, issued on 02-25-2016) and were in accordance with principles declared in Directive 2010/63/EU of the European Parliament and of the Council from 22 September 2010 on the protection of animals used for scientific purposes (revising Directive 86/609/EEC).

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Ćuruvija, I., Stanojević, S., Arsenović-Ranin, N. et al. Sex Differences in Macrophage Functions in Middle-Aged Rats: Relevance of Estradiol Level and Macrophage Estrogen Receptor Expression. Inflammation 40, 1087–1101 (2017). https://doi.org/10.1007/s10753-017-0551-3

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