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8. Zinc Deficiency Exacerbates Lead-Induced Interleukin-2 Suppression by Regulating CREM Expression.

Author

Trojan, Hannah E., Rink, Lothar, and Jakobs, Jana

Subjects
*LEAD exposure, *POISONS, *TRANSCRIPTION factors, *LEAD, *HEAVY metals
Abstract

Lead, a prevalent heavy metal, impairs the immune system by affecting T cell function. Similarly, zinc deficiency adversely affects T cells, with zinc deficiency and lead exposure being linked to reduced interleukin-2 (IL-2) production. Zinc deficiency has been associated with increased expression of the transcription factor CREM 100 kDa, which downregulates IL-2. Previous research suggests zinc may mitigate lead's toxic effects. This study explored the molecular mechanism underlying IL-2 reduction in lead-exposed T cells and examined the role of zinc status. The effects of lead exposure were investigated in Jurkat T cells in zinc-adequate, zinc-deficient, and zinc-supplemented conditions. Results showed that lead exposure increased CREM 100 kDa expression, which was amplified under zinc-deficient conditions. Consequently, IL-2 production was significantly lower in cells exposed to both lead and zinc deficiency compared to lead exposure alone. However, zinc supplementation counteracted these effects, preventing CREM 100 kDa overexpression and restoring IL-2 levels. In conclusion, we identified CREM 100 kDa as a potential molecular mechanism behind the lead-induced IL-2 decrease in Jurkat T cells, with zinc deficiency exacerbating this effect. These findings highlight the protective role of zinc in counteracting lead toxicity and emphasize the importance of maintaining adequate zinc levels for immune health. [ABSTRACT FROM AUTHOR]

Published
2025
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18. Contributors

Author

Aaseth, Jan, primary, Aggett, Peter, additional, Aitio, Antero, additional, Åkesson, Agneta, additional, Albin, Maria, additional, Alexander, Jan, additional, Andersen, Christian B.I., additional, Andersen, Ole, additional, Apostoli, Pietro, additional, Aschner, Michael, additional, Bakadlag, Rowa, additional, Barregard, Lars, additional, Bellinger, David C., additional, Bergdahl, Ingvar A., additional, Berlinger, Balazs, additional, Bernard, Alfred, additional, Bigert, Carolina, additional, Bjerregaard, Poul, additional, Blain, Robyn, additional, Blomqvist, Lennart K., additional, Bocca, Beatrice, additional, Bose-O'Reilly, Stephan, additional, Broberg, Karin, additional, Brown, Ronald P., additional, Budtz-Jørgensen, Esben, additional, Caito, Samuel W., additional, Carle, Tiffany, additional, Chen, Chien-Jen, additional, Chen, Xiao, additional, Chen, Lung-Chi, additional, Chou, C.-H. Selene J., additional, Cohen, Mitchell D., additional, Costa, Max, additional, De Palma, Giuseppe, additional, Elder, Alison, additional, Elinder, Carl-Gustaf, additional, Fadeel, Bengt, additional, Faroon, Obaid M., additional, Fowler, Bruce A., additional, Fujishiro, Hitomi, additional, Fustinoni, Silvia, additional, Gerhardsson, Lars, additional, Grandjean, Philippe, additional, Gustavsson, Per, additional, Hedberg, Yolanda, additional, Himeno, Seiichiro, additional, Huang, Xi, additional, Hultman, Per A., additional, Iavicoli, Ivo, additional, Jin, Taiyi, additional, Jones, Robert L., additional, Karlsson, Hanna L., additional, Keith, Larry S., additional, Kim, Yangho, additional, Klein, Catherine B., additional, Kleinman, Michael, additional, Kotelchuck, David, additional, Kusaka, Yukinori, additional, Landrigan, Philip J., additional, Leffler, Per E., additional, Leso, Veruscka, additional, Li, Alex Heng, additional, Lison, Dominique, additional, Liu, Shan, additional, Lucchini, Roberto G., additional, Maciejczyk, Polina, additional, Mann, Koren K., additional, Maples-Reynolds, Nikki, additional, Maroney, Michael J., additional, Martins, Airton C., additional, Matsui, Mary S., additional, Moffett, Daphne B., additional, Møller, Lisbeth Birk, additional, Mumtaz, M. Moiz, additional, Nakano, Makiko, additional, Nemery, Benoit, additional, Nogawa, Koji, additional, Nordberg, Gunnar F., additional, Nordberg, Monica, additional, Ortiz, Angelica, additional, Oskarsson, Agneta, additional, Ostrakhovitch, Elena A., additional, Pałczyński, Cezary M., additional, Pawlas, Natalia, additional, Pelclova, Daniela, additional, Pesonen, Maria, additional, Pollard, K. Michael, additional, Rink, Lothar, additional, Ruggieri, Flavia, additional, Ruiz, Patricia, additional, Sandstead, Harold H., additional, Santonen, Tiina, additional, Sato, Kazuhiro, additional, Satoh, Hiroshi, additional, Saxena, Deepak, additional, Schoeters, Greet, additional, Sjögren, Bengt, additional, Skerfving, Staffan, additional, Smith, Donald R., additional, Sullivan, Dexter W., additional, Sumi, Daigo, additional, Sun, Hong, additional, Suojalehto, Hille, additional, Tanaka, Akiyo, additional, Tenenbein, Milton, additional, Thurston, George D., additional, Tomei Torres, Francisco A., additional, Toprak, Muhammet S., additional, Tylenda, Carolyn A., additional, Tyson, Julian F., additional, Umemura, Tomohiro, additional, Whittaker, Margaret H., additional, Wolf, Jana, additional, Yan, Wenbo, additional, Yokel, Robert A., additional, and Zalups, Rudolfs K., additional

Published
2022
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19. Zinc

Author

Wolf, Jana, primary, Sandstead,, Harold H., additional, and Rink, Lothar, additional

Published
2022
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34. Molecular Hydrogen and Extracorporeal Gas Exchange: A Match Made in Heaven? An In Vitro Pilot Study.

Author

Mouzakis, Foivos Leonidas, Hima, Flutura, Kashefi, Ali, Greven, Johannes, Rink, Lothar, van der Vorst, Emiel P. C., Jankowski, Joachim, Mottaghy, Khosrow, and Spillner, Jan

Subjects
GAS mixtures, EXTRACORPOREAL membrane oxygenation, ARTIFICIAL blood circulation, CARDIOPULMONARY bypass, OXIDATIVE stress
Abstract

Extracorporeal circulation (ECC) is frequently implemented in a vast array of modalities such as hemodialysis, cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), and others. Patients receiving any such therapy are frequently encumbered with chronic inflammation, which is inherently accompanied by oxidative stress. However, ECC treatments themselves are also responsible for sustaining or promoting inflammation. On these grounds, an in vitro study was designed to investigate the therapeutic potential of molecular hydrogen (H2) against pro-inflammatory agents in ECC settings. Five miniature ECMO circuits and a small vial (Control) were primed with heparinized blood from healthy adult donors (n = 7). Three of the ECMO systems were injected with lipopolysaccharide (LPS), out of which one was additionally treated with an H2 gas mixture. After 6 h, samples were drawn for the assessment of specific biomarkers (MCP-1, MPO, MDA-a, TRX1, and IL-6). Preliminary results indicate a progressive oxidative and inflammatory response between the six systems. Circulation has triggered inflammation and blood trauma, but the staggering influence of LPS in this outcome is indisputable. Accordingly, hydrogen's remedial potential becomes immediately apparent as biomarker concentrations tend to be lower in the H2-handled circuit. Future research should have distinct objectives (e.g., dosage/duration/cycle of hydrogen administration) in order to ascertain the optimal protocol for patient treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Zinc Deficiency and Zinc Supplementation in Allergic Diseases.

Author

Maywald, Martina and Rink, Lothar

Subjects
*FOOD allergy, *ALLERGIES, *ATOPIC dermatitis, *ALLERGIC rhinitis, *DIETARY fiber, *ZINC
Abstract

In recent decades, it has become clear that allergic diseases are on the rise in both Western and developing countries. The exact reason for the increase in prevalence has not been conclusively clarified yet. Multidimensional approaches are suspected in which diet and nutrition seem to play a particularly important role. Allergic diseases are characterized by a hyper-reactive immune system to usually harmless allergens, leading to chronic inflammatory diseases comprising respiratory diseases like asthma and allergic rhinitis (AR), allergic skin diseases like atopic dermatitis (AD), and food allergies. There is evidence that diet can have a positive or negative influence on both the development and severity of allergic diseases. In particular, the intake of the essential trace element zinc plays a very important role in modulating the immune response, which was first demonstrated around 60 years ago. The most prevalent type I allergies are mainly based on altered immunoglobulin (Ig)E and T helper (Th)2 cytokine production, leading to type 2 inflammation. This immune status can also be observed during zinc deficiency and can be positively influenced by zinc supplementation. The underlying immunological mechanisms are very complex and multidimensional. Since zinc supplements vary in dose and bioavailability, and clinical trials often differ in design and structure, different results can be observed. Therefore, different results are not surprising. However, the current literature suggests a link between zinc deficiency and the development of allergies, and shows positive effects of zinc supplementation on modulating the immune system and reducing allergic symptoms, which are discussed in more detail in this review. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Zinc Toxicity: Understanding the Limits.

Author

Schoofs, Hannah, Schmit, Joyce, and Rink, Lothar

Abstract

Zinc, a vital trace element, holds significant importance in numerous physiological processes within the body. It participates in over 300 enzymatic reactions, metabolic functions, regulation of gene expression, apoptosis and immune modulation, thereby demonstrating its essential role in maintaining overall health and well-being. While zinc deficiency is associated with significant health risks, an excess of this trace element can also lead to harmful effects. According to the World Health Organization (WHO), 6.7 to 15 mg per day are referred to be the dietary reference value. An excess of the recommended daily intake may result in symptoms such as anemia, neutropenia and zincinduced copper deficiency. The European Food Safety Authority (EFSA) defines the tolerable upper intake level (UL) as 25 mg per day, whereas the Food and Drug Administration (FDA) allows 40 mg per day. This review will summarize the current knowledge regarding the calculation of UL and other health risks associated with zinc. For example, zinc intake is not limited to oral consumption; other routes, such as inhalation or topical application, may also pose risks of zinc intoxication. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Contributors

Author

Aaseth, Jan, primary, Aggett, Peter, additional, Aitio, Antero, additional, Åkesson, Agneta, additional, Albin, Maria, additional, Alexander, Jan, additional, Andersen, Christian B.I., additional, Andersen, Ole, additional, Apostoli, Pietro, additional, Aschner, Michael, additional, Bakadlag, Rowa, additional, Barregard, Lars, additional, Bellinger, David C., additional, Bergdahl, Ingvar A., additional, Berlinger, Balazs, additional, Bernard, Alfred, additional, Bigert, Carolina, additional, Bjerregaard, Poul, additional, Blain, Robyn, additional, Blomqvist, Lennart K., additional, Bocca, Beatrice, additional, Bose-O'Reilly, Stephan, additional, Broberg, Karin, additional, Brown, Ronald P., additional, Budtz-Jørgensen, Esben, additional, Caito, Samuel W., additional, Carle, Tiffany, additional, Chen, Chien-Jen, additional, Chen, Xiao, additional, Chen, Lung-Chi, additional, Chou, C.-H. Selene J., additional, Cohen, Mitchell D., additional, Costa, Max, additional, De Palma, Giuseppe, additional, Elder, Alison, additional, Elinder, Carl-Gustaf, additional, Fadeel, Bengt, additional, Faroon, Obaid M., additional, Fowler, Bruce A., additional, Fujishiro, Hitomi, additional, Fustinoni, Silvia, additional, Gerhardsson, Lars, additional, Grandjean, Philippe, additional, Gustavsson, Per, additional, Hedberg, Yolanda, additional, Himeno, Seiichiro, additional, Huang, Xi, additional, Hultman, Per A., additional, Iavicoli, Ivo, additional, Jin, Taiyi, additional, Jones, Robert L., additional, Karlsson, Hanna L., additional, Keith, Larry S., additional, Kim, Yangho, additional, Klein, Catherine B., additional, Kleinman, Michael, additional, Kotelchuck, David, additional, Kusaka, Yukinori, additional, Landrigan, Philip J., additional, Leffler, Per E., additional, Leso, Veruscka, additional, Li, Alex Heng, additional, Lison, Dominique, additional, Liu, Shan, additional, Lucchini, Roberto G., additional, Maciejczyk, Polina, additional, Mann, Koren K., additional, Maples-Reynolds, Nikki, additional, Maroney, Michael J., additional, Martins, Airton C., additional, Matsui, Mary S., additional, Moffett, Daphne B., additional, Møller, Lisbeth Birk, additional, Mumtaz, M. Moiz, additional, Nakano, Makiko, additional, Nemery, Benoit, additional, Nogawa, Koji, additional, Nordberg, Gunnar F., additional, Nordberg, Monica, additional, Ortiz, Angelica, additional, Oskarsson, Agneta, additional, Ostrakhovitch, Elena A., additional, Pałczyński, Cezary M., additional, Pawlas, Natalia, additional, Pelclova, Daniela, additional, Pesonen, Maria, additional, Pollard, K. Michael, additional, Rink, Lothar, additional, Ruggieri, Flavia, additional, Ruiz, Patricia, additional, Sandstead, Harold H., additional, Santonen, Tiina, additional, Sato, Kazuhiro, additional, Satoh, Hiroshi, additional, Saxena, Deepak, additional, Schoeters, Greet, additional, Sjögren, Bengt, additional, Skerfving, Staffan, additional, Smith, Donald R., additional, Sullivan, Dexter W., additional, Sumi, Daigo, additional, Sun, Hong, additional, Suojalehto, Hille, additional, Tanaka, Akiyo, additional, Tenenbein, Milton, additional, Thurston, George D., additional, Tomei Torres, Francisco A., additional, Toprak, Muhammet S., additional, Tylenda, Carolyn A., additional, Tyson, Julian F., additional, Umemura, Tomohiro, additional, Whittaker, Margaret H., additional, Wolf, Jana, additional, Yan, Wenbo, additional, Yokel, Robert A., additional, and Zalups, Rudolfs K., additional

Published
2021
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