TY  - JOUR
AU  - Đuretić, Jasmina
AU  - Dimitrijević, Mirjana
AU  - Stojanović, Marija
AU  - Kotur-Stevuljević, Jelena
AU  - Hamblin, Michael R.
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
AU  - Leposavić, Gordana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3781
AB  - The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (−IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with −IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.
PB  - Nature Research
T2  - Scientific Reports
T1  - Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis
VL  - 11
IS  - 1
DO  - 10.1038/s41598-021-81999-7
ER  - 

@article{
author = "Đuretić, Jasmina and Dimitrijević, Mirjana and Stojanović, Marija and Kotur-Stevuljević, Jelena and Hamblin, Michael R. and Micov, Ana and Stepanović-Petrović, Radica and Leposavić, Gordana",
year = "2021",
abstract = "The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (−IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with −IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.",
publisher = "Nature Research",
journal = "Scientific Reports",
title = "Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis",
volume = "11",
number = "1",
doi = "10.1038/s41598-021-81999-7"
}

Đuretić, J., Dimitrijević, M., Stojanović, M., Kotur-Stevuljević, J., Hamblin, M. R., Micov, A., Stepanović-Petrović, R.,& Leposavić, G.. (2021). Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis. in Scientific Reports
Nature Research., 11(1).
https://doi.org/10.1038/s41598-021-81999-7

Đuretić J, Dimitrijević M, Stojanović M, Kotur-Stevuljević J, Hamblin MR, Micov A, Stepanović-Petrović R, Leposavić G. Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis. in Scientific Reports. 2021;11(1).
doi:10.1038/s41598-021-81999-7 .

Đuretić, Jasmina, Dimitrijević, Mirjana, Stojanović, Marija, Kotur-Stevuljević, Jelena, Hamblin, Michael R., Micov, Ana, Stepanović-Petrović, Radica, Leposavić, Gordana, "Infrared radiation from cage bedding moderates rat inflammatory and autoimmune responses in collagen-induced arthritis" in Scientific Reports, 11, no. 1 (2021),
https://doi.org/10.1038/s41598-021-81999-7 . .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Bufan, Biljana
AU  - Stojanović, Marija
AU  - Leposavić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3529
AB  - The study investigated influence of sex and age on splenic myeloid dendritic cells (DCs) from Dark Agouti rats. Freshly isolated DCs from young males exhibited less mature phenotype and greater endocytic capacity compared with those from age-matched females. Upon LPS stimulation in vitro they were less potent in stimulating allogeneic CD4+ cells in mixed leukocyte reaction (MLR), due to lower expression of MHC II, and greater NO and IL-10 production. In accordance with higher TGF-β production, young male rat DCs were less potent in stimulating IL-17 production in MLR than those from young females. Irrespective of sex, endocytic capacity and responsiveness of DCs to LPS stimulation in culture, judging by their allostimulatory capacity in MLR decreased with age, reflecting decline in MHC II surface density followed by their greater NO production; the effects more prominent in females. Additionally, compared with LPS-stimulated DCs from young rats, those from sex-matched aged rats were more potent in stimulating IL-10 production in MLR, whereas capacity of DCs from aged female and male rats to stimulate IL-17 production remained unaltered and decreased, respectively. This reflected age-related shift in IL-6/TGF-β production level ratio in LPS-stimulated DC cultures towards TGF-β, and sex-specific age-related remodeling CD4+ cell cytokine pathways. Additionally, compared with LPS-stimulated DCs from young rats, those cells from sex-matched aged rats were less potent in stimulating IFN-γ production in MLR, the effect particularly prominent in MLRs encompassing male rat DCs. The study showed that stimulatory and polarizing capacity of DCs depends on rat sex and age.
PB  - Springer Nature
T2  - Biogerontology
T1  - Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells
VL  - 21
IS  - 1
SP  - 83
EP  - 107
DO  - 10.1007/s10522-019-09845-y
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Bufan, Biljana and Stojanović, Marija and Leposavić, Gordana",
year = "2020",
abstract = "The study investigated influence of sex and age on splenic myeloid dendritic cells (DCs) from Dark Agouti rats. Freshly isolated DCs from young males exhibited less mature phenotype and greater endocytic capacity compared with those from age-matched females. Upon LPS stimulation in vitro they were less potent in stimulating allogeneic CD4+ cells in mixed leukocyte reaction (MLR), due to lower expression of MHC II, and greater NO and IL-10 production. In accordance with higher TGF-β production, young male rat DCs were less potent in stimulating IL-17 production in MLR than those from young females. Irrespective of sex, endocytic capacity and responsiveness of DCs to LPS stimulation in culture, judging by their allostimulatory capacity in MLR decreased with age, reflecting decline in MHC II surface density followed by their greater NO production; the effects more prominent in females. Additionally, compared with LPS-stimulated DCs from young rats, those from sex-matched aged rats were more potent in stimulating IL-10 production in MLR, whereas capacity of DCs from aged female and male rats to stimulate IL-17 production remained unaltered and decreased, respectively. This reflected age-related shift in IL-6/TGF-β production level ratio in LPS-stimulated DC cultures towards TGF-β, and sex-specific age-related remodeling CD4+ cell cytokine pathways. Additionally, compared with LPS-stimulated DCs from young rats, those cells from sex-matched aged rats were less potent in stimulating IFN-γ production in MLR, the effect particularly prominent in MLRs encompassing male rat DCs. The study showed that stimulatory and polarizing capacity of DCs depends on rat sex and age.",
publisher = "Springer Nature",
journal = "Biogerontology",
title = "Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells",
volume = "21",
number = "1",
pages = "83-107",
doi = "10.1007/s10522-019-09845-y"
}

Stojić-Vukanić, Z., Pilipović, I., Bufan, B., Stojanović, M.,& Leposavić, G.. (2020). Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells. in Biogerontology
Springer Nature., 21(1), 83-107.
https://doi.org/10.1007/s10522-019-09845-y

Stojić-Vukanić Z, Pilipović I, Bufan B, Stojanović M, Leposavić G. Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells. in Biogerontology. 2020;21(1):83-107.
doi:10.1007/s10522-019-09845-y .

Stojić-Vukanić, Zorica, Pilipović, Ivan, Bufan, Biljana, Stojanović, Marija, Leposavić, Gordana, "Age and sex determine CD4+ T cell stimulatory and polarizing capacity of rat splenic dendritic cells" in Biogerontology, 21, no. 1 (2020):83-107,
https://doi.org/10.1007/s10522-019-09845-y . .

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Stojanović, Marija
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3221
AB  - An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression. Additionally, immunization diminished the expression of Thy-1, a negative regulator of TCR alpha beta-mediated signaling and activation thresholds, on CD4+CD8+ TCR alpha beta(lo/hi) thymocytes undergoing selection and thereby impaired thymocyte selection/survival. This diminished the generation of mature CD4+ and CD8+ single positive TCR alpha beta(hi) thymocytes and, consequently, CD4+ and CD8+ recent thymic emigrants. In immunized rats, thymic differentiation of natural regulatory CD4+Foxp3+CD25+ T cells (nTregs) was particularly affected reflecting a diminished expression of IL-7, IL-2 and IL-15. The decline in the overall thymic T-cell output and nTreg generation was more pronounced in DA than AO rats. Additionally, differently from immunized AO rats, in DA ones the frequency of CD28- cells secreting cytolytic enzymes within peripheral blood CD4+ T lymphocytes increased, as a consequence of thymic atrophy-related replicative stress (mirrored in CD4+ cell memory pool expansion and p16(INK4a) accumulation). The higher circulating level of TNF-alpha in DA compared with AO rats could also contribute to this difference. Consistently, higher frequency of cytolytic CD4+ granzyme B+ cells (associated with greater tissue damage) was found in spinal cord of immunized DA rats compared with their AO counterparts. In conclusion, the study indicated that strain differences in immunization-induced changes in thymopoiesis and peripheral CD4+CD28- T-cell generation could contribute to rat strain-specific clinical outcomes of immunization for EAE.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization
VL  - 13
IS  - 8
DO  - 10.1371/journal.pone.0201848
ER  - 

@article{
author = "Nacka-Aleksić, Mirjana and Stojanović, Marija and Pilipović, Ivan and Stojić-Vukanić, Zorica and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "An accumulating body of evidence suggests that development of autoimmune pathologies leads to thymic dysfunction and changes in peripheral T-cell compartment, which, in turn, perpetuate their pathogenesis. To test this hypothesis, thymocyte differentiation/maturation in rats susceptible (Dark Agouti, DA) and relatively resistant (Albino Oxford, AO) to experimental autoimmune encephalomyelitis (EAE) induction was examined. Irrespective of strain, immunization for EAE (i) increased the circulating levels of IL-6, a cytokine causally linked with thymic atrophy, and (ii) led to thymic atrophy reflecting partly enhanced thymocyte apoptosis associated with downregulated thymic IL-7 expression. Additionally, immunization diminished the expression of Thy-1, a negative regulator of TCR alpha beta-mediated signaling and activation thresholds, on CD4+CD8+ TCR alpha beta(lo/hi) thymocytes undergoing selection and thereby impaired thymocyte selection/survival. This diminished the generation of mature CD4+ and CD8+ single positive TCR alpha beta(hi) thymocytes and, consequently, CD4+ and CD8+ recent thymic emigrants. In immunized rats, thymic differentiation of natural regulatory CD4+Foxp3+CD25+ T cells (nTregs) was particularly affected reflecting a diminished expression of IL-7, IL-2 and IL-15. The decline in the overall thymic T-cell output and nTreg generation was more pronounced in DA than AO rats. Additionally, differently from immunized AO rats, in DA ones the frequency of CD28- cells secreting cytolytic enzymes within peripheral blood CD4+ T lymphocytes increased, as a consequence of thymic atrophy-related replicative stress (mirrored in CD4+ cell memory pool expansion and p16(INK4a) accumulation). The higher circulating level of TNF-alpha in DA compared with AO rats could also contribute to this difference. Consistently, higher frequency of cytolytic CD4+ granzyme B+ cells (associated with greater tissue damage) was found in spinal cord of immunized DA rats compared with their AO counterparts. In conclusion, the study indicated that strain differences in immunization-induced changes in thymopoiesis and peripheral CD4+CD28- T-cell generation could contribute to rat strain-specific clinical outcomes of immunization for EAE.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization",
volume = "13",
number = "8",
doi = "10.1371/journal.pone.0201848"
}

Nacka-Aleksić, M., Stojanović, M., Pilipović, I., Stojić-Vukanić, Z., Kosec, D.,& Leposavić, G.. (2018). Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization. in PLoS One
Public Library Science, San Francisco., 13(8).
https://doi.org/10.1371/journal.pone.0201848

Nacka-Aleksić M, Stojanović M, Pilipović I, Stojić-Vukanić Z, Kosec D, Leposavić G. Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization. in PLoS One. 2018;13(8).
doi:10.1371/journal.pone.0201848 .

Nacka-Aleksić, Mirjana, Stojanović, Marija, Pilipović, Ivan, Stojić-Vukanić, Zorica, Kosec, Duško, Leposavić, Gordana, "Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization" in PLoS One, 13, no. 8 (2018),
https://doi.org/10.1371/journal.pone.0201848 . .

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Stojanović, Marija
AU  - Simić, Lidija
AU  - Bufan, Biljana
AU  - Kotur-Stevuljević, Jelena
AU  - Stojić-Vukanić, Zorica
AU  - Dimitrijević, Mirjana
AU  - Ražić, Slavica
AU  - Leposavić, Gordana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2795
AB  - To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2-3 month-old (young) and 18-20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1 beta (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1 beta (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1 beta expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1 beta expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.
PB  - Springer, New York
T2  - Biogerontology
T1  - Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state
VL  - 18
IS  - 5
SP  - 821
EP  - 839
DO  - 10.1007/s10522-017-9726-4
ER  - 

@article{
author = "Nacka-Aleksić, Mirjana and Stojanović, Marija and Simić, Lidija and Bufan, Biljana and Kotur-Stevuljević, Jelena and Stojić-Vukanić, Zorica and Dimitrijević, Mirjana and Ražić, Slavica and Leposavić, Gordana",
year = "2017",
abstract = "To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2-3 month-old (young) and 18-20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1 beta (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1 beta (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1 beta expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1 beta expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.",
publisher = "Springer, New York",
journal = "Biogerontology",
title = "Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state",
volume = "18",
number = "5",
pages = "821-839",
doi = "10.1007/s10522-017-9726-4"
}

Nacka-Aleksić, M., Stojanović, M., Simić, L., Bufan, B., Kotur-Stevuljević, J., Stojić-Vukanić, Z., Dimitrijević, M., Ražić, S.,& Leposavić, G.. (2017). Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state. in Biogerontology
Springer, New York., 18(5), 821-839.
https://doi.org/10.1007/s10522-017-9726-4

Nacka-Aleksić M, Stojanović M, Simić L, Bufan B, Kotur-Stevuljević J, Stojić-Vukanić Z, Dimitrijević M, Ražić S, Leposavić G. Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state. in Biogerontology. 2017;18(5):821-839.
doi:10.1007/s10522-017-9726-4 .

Nacka-Aleksić, Mirjana, Stojanović, Marija, Simić, Lidija, Bufan, Biljana, Kotur-Stevuljević, Jelena, Stojić-Vukanić, Zorica, Dimitrijević, Mirjana, Ražić, Slavica, Leposavić, Gordana, "Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state" in Biogerontology, 18, no. 5 (2017):821-839,
https://doi.org/10.1007/s10522-017-9726-4 . .