| First Author | Haase H | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 9 | Pages | 6491-502 |
| PubMed ID | 18941240 | Mgi Jnum | J:140718 |
| Mgi Id | MGI:3814469 | Doi | 10.4049/jimmunol.181.9.6491 |
| Citation | Haase H, et al. (2008) Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes. J Immunol 181(9):6491-502 |
| abstractText | 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 (Zn(2+)), but this still awaits experimental verification. Zn(2+) 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-alpha. Here we demonstrate that these effects are due to a physiological signaling system involving intracellular Zn(2+) signals. An increase of the intracellular zinc ion concentration occurs upon stimulation of human leukocytes with Escherichia coli, LPS, Pam(3)CSK(4), TNF-alpha, 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-kappaB, and abrogates the release of proinflammatory cytokines, including TNF-alpha. This function of Zn(2+) 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 Ca(2+). |
