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Dimitrijevic M.,Institute of Virology Vaccines and Sera Torlak | Stanojevic S.,Institute of Virology Vaccines and Sera Torlak | Kustrimovic N.,Institute of Virology Vaccines and Sera Torlak | Mitic K.,Institute of Virology Vaccines and Sera Torlak | And 4 more authors.
Experimental Gerontology | Year: 2013

The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2high cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. © 2013 Elsevier Inc. Source


Ivanovic N.,University of Belgrade | Minic R.,Institute of Virology Vaccines and Sera Torlak | Dimitrijevic L.,Institute of Virology Vaccines and Sera Torlak | Radojevic Skodric S.,University of Belgrade | And 2 more authors.
Food and Function | Year: 2015

In this study, two Lactobacillus strains (L. rhamnosus LA68 and L. plantarum WCFS1) were evaluated for their effects on high fat diet induced pathology in mice. The aim was to determine whether the administration of lactic acid bacteria had beneficial effects on ameliorating pathology. C57BL/6 mice fed a high fat diet were orally administered with the Lactobacillus strains. Both the metabolic and immunological parameters were analyzed. The administration of both of the strains had beneficial effects on mouse weight, serum cholesterol, TNF-α levels and liver histology. LA68 lowered the total cholesterol and HDL levels more prominently, whereas WCFS1 was more potent in lowering the TG and LDL levels. Leptin and adiponectin levels were increased in all experimental groups to different extents. The administration of L. plantarum WCFS1 led to a marked increase in leptin levels, as well as an increase in CD3+CD4+ and CD3+CD8+ cells, and a decrease of CD25+ cells, and had a lowering effect on IL-6 production and cell metabolic activity. In conclusion, active administration of both Lactobacillus strains had a positive effect on HFD-induced pathology. Although both of the tested strains had beneficial effects, oral administration of WCFS1 increased leptin levels and had a more prominent immunomodulatory effect, which should be taken into consideration in case of humane usage. This journal is © The Royal Society of Chemistry 2015. Source


Pilipovic I.,Institute of Virology Vaccines and Sera Torlak | Radojevic K.,Institute of Virology Vaccines and Sera Torlak | Perisic M.,Institute of Virology Vaccines and Sera Torlak | Kosec D.,Institute of Virology Vaccines and Sera Torlak | And 3 more authors.
Experimental Physiology | Year: 2012

Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and β2- and α1B-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine β-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of β2- and α1B-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg-1 day-1, s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine β-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of α1B-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society. Source

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