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Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages.

Cellular zinc homeostasis modulates polarization of THP-1-derived macrophages.
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Dierichs L, Kloubert V, Rink L,


Dierichs L, Kloubert V, Rink L, (click to view)

Dierichs L, Kloubert V, Rink L,

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European journal of nutrition 2017 07 07() doi 10.1007/s00394-017-1491-2
Abstract
PURPOSE
Polarization of macrophages by environmental stimuli leads to the characteristic of different phenotypes that exhibit distinct functions, ranging in a continuous spectrum from pro-inflammatory M1 up to immunoregulatory and wound-healing M2 macrophages. Diseases like cancer, allergic asthma or diabetes are associated with an M1/M2 imbalance. Owing to the importance of the essential trace element zinc for the immune system and its involvement in signal transduction as a second messenger, we investigated the impact of zinc on M1 and M2 polarization of macrophages in vitro.

METHODS
A polarization model with human THP-1 cells was established and validated with previously described markers using quantitative real-time PCR, Western blot and flow cytometry. Intracellular free Zn(2+) was determined with FluoZin-3-AM.

RESULTS
Whereas pSTAT1 and HLA-DR or pSTAT6 and Dectin-1 distinguish between M1 and M2 macrophages, respectively, CD86 and CD206 failed. Depending on the used markers, both zinc supplementation in physiological dose (50 µM) and zinc deficiency promote M1 polarization of THP-1-derived macrophages. Furthermore, zinc supplementation strongly inhibits M2 polarization.

CONCLUSION
For the first time, we show a modulating effect of zinc for the polarization of human macrophages. The strong inhibitory effect of zinc supplementation on M2 polarization indicates a relevance regarding M2-dominated diseases like allergic asthma or cancer. All in all, zinc achieves a great potential for modulating macrophage polarization.

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