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How Zinc Deficiencies Negatively Affect the Immune System- Thomas DeLauer

Zinc and Immune System

Anti-inflammatory potential of zinc

Inflammation is the major hallmark of innate immunity. One of the major inflammatory pathways is NF-kB. It was reported in the Nutrition that zinc can supress NF-kB by stimulating protein A20. This protein is recognized as anti-inflammatory molecule that prevents modulation of NF-kB by IKK. NF-kB is a transcription factor for many pro-inflammatory cytokines. Two of these cytokines, IL-1beta and TNF alfa, were found to be suppressed after zinc supplementation.

As reported in American Journal of Clinical Nutrition. Protein A20 is not the only mediator of zinc’s anti-inflammatory properties. PPAR is well-known in fasting community as it upregulates enzymes needed for fat metabolism in times of nutritional challenge. The expression of PPAR is stimulated by zinc. NF-kB acts by binding to DNA and dictates which part of the DNA should be expressed. PPAR inhibits the binding of NF-KB to DNA and prevents the activation of pro-inflammatory genes.

Granulocytes

To examine the importance of zinc, researchers are using zinc chelators which disable the utilization of zinc. Study published in Biological Trace Element Research proved that ZD is detrimental for granulocytes functioning. However, zinc excess was shown to impair the function as well. These results signify the importance of correct dosing.

The production of ROS is dependent on enzyme NADPH. Zinc is an inhibitor of NADPH and prevents excessive damage from ROS. On the contrary, excessive zinc concentrations can block the capacity to produce ROS and impair the elimination of the pathogen.

Macrophages

Zinc has an important regulatory function in cells of the innate immunity, particularly in macrophages. The NF-kB is in the centre of the mechanism again. After activation of NF-kB expression of zinc transporter ZIP8 is increased. More zinc can get to the cell and as mentioned earlier, zinc is preventing the binding of NF-kB to DNA and reduces the expression of pro-inflammatory cytokines.

Natural Killer Cells

Natural killer (NK) cells make up 15% of immune cells in peripheral blood. They can recognize virally infected cell or cancer cell. For optimal functioning of the organism these cells must be destroyed, hence the “killer” name. Immune cells are dependent on communication between each other. NK cells are stimulated by cytokine IL-2 secreted by T cell. In a study published in the Journal of Laboratory and Clinical Medicine, the production of IL-2 is decreased during ZD, resulting in the compromised activity of NK cells.

Membrane Barriers

Immunity our cells don't depend not only on cells, same as soldiers (immune cells) defending a castle are dependent on a fortress, our body is dependent on the barrier of epithelial cells of lungs and intestine. The epithelium is a series of cell bound tightly to each other to prevent the entry of foreign particles. The close contact of these cells is dependent on protein complexes called tight junctions and adherens junctions. In the study from the Journal of Nutrition, in zinc deprived cells, faster degradation of two structural proteins, E-cadherin and β-catenin, was observed. Supplementation can restore the integrity and function of membrane barriers.

References

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