The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes
Abstract
Cytosolic alterations of calcium ion concentrations are an integral part of signal transduction. Similar functions have been hypothesized for other metal ions, in particular zinc (Zn2+), but this still awaits experimental verification. Zn2+ is important for multiple cellular functions, especially in the immune system. Among other effects, it influences formation and secretion of pro-inflammatory cytokines, including TNF-α. Here we demonstrate that these effects are due to a physiological signaling system involving intracellular Zn2+ signals. An increase of the intracellular zinc ion concentration occurs upon stimulation of human leukocytes with Escherichia coli, LPS, Pam3CSK4, TNF-α, or insulin, predominantly in monocytes. Chelating this zinc signal with the membrane permeable zinc-specific chelator TPEN (N,N,N′,N′-tetrakis-(2-pyridyl-methyl)ethylenediamine) completely blocks activation of LPS-induced signaling pathways involving p38 MAPK, ERK1/2, and NF-κB, and abrogates the release of proinflammatory cytokines, including TNF-α. This function of Zn2+ is not limited to monocytes or even the immune system, but seems to be another generalized signaling system based on intracellular fluctuations of metal ion concentrations, acting parallel to Ca2+.
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Cites
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Zinc transporters and the cellular trafficking of zinc
Eide, D. J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.03.005 · Cited by 874
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MAP kinase phosphatase 1 controls innate immune responses and suppresses endotoxic shock
Zhao, Q., Wang, X., Nelin, L. D., Yao, Y., Matta, R., Manson, M. E., Baliga, R. S., Meng, X., Smith, C. V., Bauer, J. A., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051794 · Cited by 370
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Kambe, T., Tsuji, T., Hashimoto, A., & Itsumura, N. (2015) · Physiological Reviews · doi:10.1152/physrev.00035.2014 · Cited by 1,158
Zinc in Wound Healing Modulation
Lin, P.-H., Sermersheim, M., Li, H., Lee, P. H. U., Steinberg, S. M., & Ma, J. (2017) · Nutrients · doi:10.3390/nu10010016 · Cited by 643
The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens
Djoko, K. Y., Ong, C.-L. Y., Walker, M. J., & McEwan, A. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.647099 · Cited by 417
The immune system and the impact of zinc during aging
Haase, H., & Rink, L. (2009) · Immunity & Ageing · doi:10.1186/1742-4933-6-9 · Cited by 334
Self-citationMaywald, M., Wessels, I., & Rink, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102222 · Cited by 309
Multiple impacts of zinc on immune function
Haase, H., & Rink, L. (2014) · Metallomics · doi:10.1039/c3mt00353a · Cited by 237
Self-citationZinc transporter ZIP8 (SLC39A8) and zinc influence IFN-γ expression in activated human T cells
Aydemir, T. B., Liuzzi, J. P., McClellan, S., & Cousins, R. J. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208759 · Cited by 229
Regulation of T cell receptor signaling by activation-induced zinc influx
Yu, M., Lee, W.-W., Tomar, D., Pryshchep, S., Czesnikiewicz-Guzik, M., Lamar, D. L., Li, G., Singh, K., Tian, L., Weyand, C. M., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20100031 · Cited by 153
Kapetanovic, R., Bokil, N. J., Achard, M. E. S., Ong, C. Y., Peters, K. M., Stocks, C. J., Phan, M., Monteleone, M., Schroder, K., Irvine, K. M., et al. (2016) · The FASEB Journal · doi:10.1096/fj.201500061 · Cited by 86
The impact of metal availability on immune function during infection
Monteith, A. J., & Skaar, E. P. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.08.004 · Cited by 83
Metadata
- Authors
- Haase, H., Ober-Blöbaum, J. L., Engelhardt, G., Hebel, S., Heit, A., Heine, H., & Rink, L.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11-01
- Volume
- 181
- Issue
- 9
- Pages
- 6491-6502
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1531010890
- Cited by
- 286
- References
- 4
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- closed
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