Cakić Milošević, Maja

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Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?

Kulaš, Jelena; Tucović, Dina; Zeljković, Milica; Popović, Dušanka; Popov Aleksandrov, Aleksandra; Ukropina, Mirela; Cakić Milošević, Maja; Glamočlija, Jasmina; Kataranovski, Milena; Mirkov, Ivana

(Elsevier Ireland Ltd, 2021)

TY  - JOUR
AU  - Kulaš, Jelena
AU  - Tucović, Dina
AU  - Zeljković, Milica
AU  - Popović, Dušanka
AU  - Popov Aleksandrov, Aleksandra
AU  - Ukropina, Mirela
AU  - Cakić Milošević, Maja
AU  - Glamočlija, Jasmina
AU  - Kataranovski, Milena
AU  - Mirkov, Ivana
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0300483X20302730
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4033
AB  - Cadmium (Cd) is one of the most toxic environmental heavy metals to which the general population is exposed mainly via the oral route. Owing to its immunomodulatory potential, orally acquired Cd affects antimicrobial immune defense in several organs, including the lungs. While there are data concerning Cd and viral and bacterial pulmonary infections, effects on fungal infections are not studied yet. In the present study, the effect of the Cd (5 mg/L for 30 days, in drinking water, the average daily Cd intake 0.641 ± 0.089 mg/kg) on the immune response of rats to pulmonary A. fumigatus infection was examined. Data obtained showed that orally acquired cadmium does not affect the elimination of the fungus in immunocompetent rats owing to the preservation of some aspects of innate immune responses (lung leukocyte infiltration and NBT reduction) and an increase in other (increased numbers of mucus-producing goblet cells, MPO release). Cd does not affect an IFN-γ response in lung leukocytes during the infection (despite suppression of cytokine production in cells of lung-draining lymph nodes), while it stimulates IL-17 and suppresses IL-10 response to the fungus. As a result, the elimination of the fungus occurs in a milieu with the prevailing proinflammatory response in Cd-exposed animals that preserved fungal elimination from the lungs, though with more intense injury to the lung tissue. Therefore, the proinflammatory microenvironment in the lungs created by Cd that sustains inflammatory/immune response to the fungus to which humans are exposed for a lifetime, raises a concern of orally acquired Cd as a risk factor for the development of chronic low-grade pulmonary inflammation.
PB  - Elsevier Ireland Ltd
T2  - Toxicology
T2  - Toxicology
T1  - Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?
VL  - 447
DO  - 10.1016/j.tox.2020.152634
SP  - 152634
ER  - 
@article{
author = "Kulaš, Jelena and Tucović, Dina and Zeljković, Milica and Popović, Dušanka and Popov Aleksandrov, Aleksandra and Ukropina, Mirela and Cakić Milošević, Maja and Glamočlija, Jasmina and Kataranovski, Milena and Mirkov, Ivana",
year = "2021",
abstract = "Cadmium (Cd) is one of the most toxic environmental heavy metals to which the general population is exposed mainly via the oral route. Owing to its immunomodulatory potential, orally acquired Cd affects antimicrobial immune defense in several organs, including the lungs. While there are data concerning Cd and viral and bacterial pulmonary infections, effects on fungal infections are not studied yet. In the present study, the effect of the Cd (5 mg/L for 30 days, in drinking water, the average daily Cd intake 0.641 ± 0.089 mg/kg) on the immune response of rats to pulmonary A. fumigatus infection was examined. Data obtained showed that orally acquired cadmium does not affect the elimination of the fungus in immunocompetent rats owing to the preservation of some aspects of innate immune responses (lung leukocyte infiltration and NBT reduction) and an increase in other (increased numbers of mucus-producing goblet cells, MPO release). Cd does not affect an IFN-γ response in lung leukocytes during the infection (despite suppression of cytokine production in cells of lung-draining lymph nodes), while it stimulates IL-17 and suppresses IL-10 response to the fungus. As a result, the elimination of the fungus occurs in a milieu with the prevailing proinflammatory response in Cd-exposed animals that preserved fungal elimination from the lungs, though with more intense injury to the lung tissue. Therefore, the proinflammatory microenvironment in the lungs created by Cd that sustains inflammatory/immune response to the fungus to which humans are exposed for a lifetime, raises a concern of orally acquired Cd as a risk factor for the development of chronic low-grade pulmonary inflammation.",
publisher = "Elsevier Ireland Ltd",
journal = "Toxicology, Toxicology",
title = "Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?",
volume = "447",
doi = "10.1016/j.tox.2020.152634",
pages = "152634"
}
Kulaš, J., Tucović, D., Zeljković, M., Popović, D., Popov Aleksandrov, A., Ukropina, M., Cakić Milošević, M., Glamočlija, J., Kataranovski, M.,& Mirkov, I.. (2021). Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?. in Toxicology
Elsevier Ireland Ltd., 447, 152634.
https://doi.org/10.1016/j.tox.2020.152634
Kulaš J, Tucović D, Zeljković M, Popović D, Popov Aleksandrov A, Ukropina M, Cakić Milošević M, Glamočlija J, Kataranovski M, Mirkov I. Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?. in Toxicology. 2021;447:152634.
doi:10.1016/j.tox.2020.152634 .
Kulaš, Jelena, Tucović, Dina, Zeljković, Milica, Popović, Dušanka, Popov Aleksandrov, Aleksandra, Ukropina, Mirela, Cakić Milošević, Maja, Glamočlija, Jasmina, Kataranovski, Milena, Mirkov, Ivana, "Proinflammatory effects of environmental cadmium boost resistance to opportunistic pathogen Aspergillus fumigatus: Implications for sustained low-level pulmonary inflammation?" in Toxicology, 447 (2021):152634,
https://doi.org/10.1016/j.tox.2020.152634 . .
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Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.

Kulaš, Jelena; Ninkov, Marina; Tucović, Dina; Popov Aleksandrov, Aleksandra; Ukropina, Mirela; Cakić Milošević, Maja; Mutić, Jelena; Kataranovski, Milena; Mirkov, Ivana

(Biomedical and Environmental Sciences, 2019)

TY  - JOUR
AU  - Kulaš, Jelena
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Ukropina, Mirela
AU  - Cakić Milošević, Maja
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
AU  - Mirkov, Ivana
PY  - 2019
UR  - http://www.besjournal.com/en/article/doi/10.3967/bes2019.068
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3470
AB  - OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.
PB  - Biomedical and Environmental Sciences
T2  - Biomedical and Environmental Sciences
T1  - Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.
IS  - 7
VL  - 32
DO  - 10.3967/bes2019.068
SP  - 508
EP  - 519
ER  - 
@article{
author = "Kulaš, Jelena and Ninkov, Marina and Tucović, Dina and Popov Aleksandrov, Aleksandra and Ukropina, Mirela and Cakić Milošević, Maja and Mutić, Jelena and Kataranovski, Milena and Mirkov, Ivana",
year = "2019",
abstract = "OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.",
publisher = "Biomedical and Environmental Sciences",
journal = "Biomedical and Environmental Sciences",
title = "Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.",
number = "7",
volume = "32",
doi = "10.3967/bes2019.068",
pages = "508-519"
}
Kulaš, J., Ninkov, M., Tucović, D., Popov Aleksandrov, A., Ukropina, M., Cakić Milošević, M., Mutić, J., Kataranovski, M.,& Mirkov, I.. (2019). Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.. in Biomedical and Environmental Sciences
Biomedical and Environmental Sciences., 32(7), 508-519.
https://doi.org/10.3967/bes2019.068
Kulaš J, Ninkov M, Tucović D, Popov Aleksandrov A, Ukropina M, Cakić Milošević M, Mutić J, Kataranovski M, Mirkov I. Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.. in Biomedical and Environmental Sciences. 2019;32(7):508-519.
doi:10.3967/bes2019.068 .
Kulaš, Jelena, Ninkov, Marina, Tucović, Dina, Popov Aleksandrov, Aleksandra, Ukropina, Mirela, Cakić Milošević, Maja, Mutić, Jelena, Kataranovski, Milena, Mirkov, Ivana, "Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats." in Biomedical and Environmental Sciences, 32, no. 7 (2019):508-519,
https://doi.org/10.3967/bes2019.068 . .
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