Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression
2014
Аутори
Bufan, BiljanaĐikić, Jasmina
Nacka-Aleksić, Mirjana
Stojić-Vukanić, Zorica
Dimitrijević, Mirjana
Leposavić, Gordana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3-month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund's adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the exp...ression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-alpha and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+: CD4-DC ratio towards CD4- cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+: CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-alpha mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1 beta (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1 beta compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.
Кључне речи:
Aging / Cytokine gene expression / Dendritic cells / Experimental autoimmune encephalomyelitis / Rat strain differencesИзвор:
Genetika, Belgrade, 2014, 46, 1, 287-301Издавач:
- Društvo genetičara Srbije, Beograd
Финансирање / пројекти:
DOI: 10.2298/GENSR1401287B
ISSN: 0534-0012
WoS: 000338930500029
Scopus: 2-s2.0-84900322668
Институција/група
PharmacyTY - JOUR AU - Bufan, Biljana AU - Đikić, Jasmina AU - Nacka-Aleksić, Mirjana AU - Stojić-Vukanić, Zorica AU - Dimitrijević, Mirjana AU - Leposavić, Gordana PY - 2014 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2087 AB - Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3-month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund's adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-alpha and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+: CD4-DC ratio towards CD4- cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+: CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-alpha mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1 beta (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1 beta compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction. PB - Društvo genetičara Srbije, Beograd T2 - Genetika, Belgrade T1 - Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression VL - 46 IS - 1 SP - 287 EP - 301 DO - 10.2298/GENSR1401287B ER -
@article{ author = "Bufan, Biljana and Đikić, Jasmina and Nacka-Aleksić, Mirjana and Stojić-Vukanić, Zorica and Dimitrijević, Mirjana and Leposavić, Gordana", year = "2014", abstract = "Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3-month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund's adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-alpha and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+: CD4-DC ratio towards CD4- cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+: CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-alpha mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1 beta (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1 beta compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.", publisher = "Društvo genetičara Srbije, Beograd", journal = "Genetika, Belgrade", title = "Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression", volume = "46", number = "1", pages = "287-301", doi = "10.2298/GENSR1401287B" }
Bufan, B., Đikić, J., Nacka-Aleksić, M., Stojić-Vukanić, Z., Dimitrijević, M.,& Leposavić, G.. (2014). Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression. in Genetika, Belgrade Društvo genetičara Srbije, Beograd., 46(1), 287-301. https://doi.org/10.2298/GENSR1401287B
Bufan B, Đikić J, Nacka-Aleksić M, Stojić-Vukanić Z, Dimitrijević M, Leposavić G. Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression. in Genetika, Belgrade. 2014;46(1):287-301. doi:10.2298/GENSR1401287B .
Bufan, Biljana, Đikić, Jasmina, Nacka-Aleksić, Mirjana, Stojić-Vukanić, Zorica, Dimitrijević, Mirjana, Leposavić, Gordana, "Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression" in Genetika, Belgrade, 46, no. 1 (2014):287-301, https://doi.org/10.2298/GENSR1401287B . .