Zinc Signaling pp 279-304 | Cite as

Zinc Signals in Inflammation



Zinc is an essential micronutrient for cell growth, differentiation, and survival and when deficient, is associated with increased susceptibility to infections and inflammatory disorders. Zinc homeostasis is critical for proper immune cell function and is therefore tightly regulated by zinc transporters. Recent evidence has highlighted zinc as an intracellular signaling molecule capable of modulating immune cell signaling. Slight changes in intracellular zinc, either by zinc deficiency or by excess zinc, can alter cellular signaling and immune cell function often resulting in increased inflammation. In this chapter, we discuss zinc signals in inflammation with a focus on zinc dependent modulation of select signaling pathways and the effects on immune cell function in response to potentially damaging challenges.


Zinc Zinc deficiency Inflammation Zinc signal Host defense Innate and adaptive immunity 


  1. Alker W, Haase H (2018) Zinc and Sepsis. Nutrients 10(8). doi: E976 [pii]
  2. Allan GM, Arroll B (2014) Prevention and treatment of the common cold: making sense of the evidence. CMAJ 186(3):190–199. Scholar
  3. Ananthakrishnan AN, Khalili H, Song M et al (2015) Zinc intake and risk of Crohn’s disease and ulcerative colitis: a prospective cohort study. Int J Epidemiol 44(6):1995–2005. Scholar
  4. Anzilotti C, Swan DJ, Boisson B et al (2019) An essential role for the Zn(2+) transporter ZIP7 in B cell development. Nat Immunol. Scholar
  5. Arroll B (2008) Common cold. BMJ Clin Evid 2008:1510. doi:1510 [pii]PubMedPubMedCentralGoogle Scholar
  6. Bafaro E, Liu Y, Xu Y et al (2017) The emerging role of zinc transporters in cellular homeostasis and cancer. Signal Transduct Target Ther 2. Epub 2017 July 28. doi:17029 [pii]
  7. Bao B, Prasad AS, Beck FW et al (2007) Zinc up-regulates NF-kappaB activation via phosphorylation of IkappaB in HUT-78 (Th0) cells. FEBS Lett 581(23):4507–4511. doi:S0014-5793(07)00906-4 [pii]CrossRefGoogle Scholar
  8. Barnett JB, Dao MC, Hamer DH et al (2016) Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 103(3):942–951. Scholar
  9. Basnet S, Mathisen M, Strand TA (2015) Oral zinc and common childhood infections--an update. J Trace Elem Med Biol 31:163–166. Scholar
  10. Bishop GM, Dringen R, Robinson SR (2007) Zinc stimulates the production of toxic reactive oxygen species (ROS) and inhibits glutathione reductase in astrocytes. Free Radic Biol Med 42(8):1222–1230. doi:S0891-5849(07)00049-4 [pii]CrossRefGoogle Scholar
  11. Blewett HJ, Taylor CG (2012) Dietary zinc deficiency in rodents: effects on T-cell development, maturation and phenotypes. Nutrients 4(6):449–466. Scholar
  12. Bonaventura P, Benedetti G, Albarede F et al (2015) Zinc and its role in immunity and inflammation. Autoimmun Rev 14(4):277–285. Scholar
  13. Bosmann M, Ward PA (2013) The inflammatory response in sepsis. Trends Immunol 34(3):129–136. Scholar
  14. Cabrera AJ (2015) Zinc, aging, and immunosenescence: an overview. Pathobiol Aging Age Relat Dis 5:25592. Scholar
  15. Cassandri M, Smirnov A, Novelli F et al (2017) Zinc-finger proteins in health and disease. Cell Death Discov 3:17071. Scholar
  16. Chen G, Lustig A, Weng NP (2013) T cell aging: a review of the transcriptional changes determined from genome-wide analysis. Front Immunol 4:121. Scholar
  17. Cheng G, Chang FJ, You PH et al (2018) ZIP8 induces monocyte adhesion to the aortas ex-vivo by regulating zinc influx. Int Immunopharmacol 62:203–211. doi:S1567-5769(18)30269-8 [pii]CrossRefGoogle Scholar
  18. Choi S, Liu X, Pan Z (2018) Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases. Acta Pharmacol Sin 39(7):1120–1132. Scholar
  19. Colomar-Carando N, Meseguer A, Company-Garrido I et al (2019) Zip6 transporter is an essential component of the lymphocyte activation machinery. J Immunol 202(2):441–450. Scholar
  20. Elliott DE, Siddique SS, Weinstock JV (2014) Innate immunity in disease. Clin Gastroenterol Hepatol 12(5):749–755. Scholar
  21. Finamore A, Massimi M, Conti Devirgiliis L et al (2008) Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 cells. J Nutr 138(9):1664–1670. doi:138/9/1664 [pii]CrossRefGoogle Scholar
  22. Fukada T, Yamasaki S, Nishida K et al (2011) Zinc homeostasis and signaling in health and diseases: zinc signaling. J Biol Inorg Chem 16(7):1123–1134. Scholar
  23. Fulop T, Larbi A, Dupuis G et al (2018) Immunosenescence and Inflamm-aging as two sides of the same coin: friends or foes? Front Immunol 8:1960. Scholar
  24. Gammoh NZ, Rink L (2017) Zinc in infection and inflammation. Nutrients 9(6):624. doi:E624 [pii]CrossRefPubMedCentralGoogle Scholar
  25. Ganatra HA, Varisco BM, Harmon K et al (2017) Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis. Innate Immun 23(1):67–76. Scholar
  26. Gao H, Dai W, Zhao L et al (2018) The role of zinc and zinc homeostasis in macrophage function. J Immunol Res 2018:6872621. Scholar
  27. George MM, Subramanian Vignesh K, Landero Figueroa JA et al (2016) Zinc induces dendritic cell Tolerogenic phenotype and skews regulatory T cell-Th17 balance. J Immunol 197(5):1864–1876. Scholar
  28. Giacconi R, Malavolta M, Costarelli L et al (2012) Comparison of intracellular zinc signals in nonadherent lymphocytes from young-adult and elderly donors: role of zinc transporters (zip family) and proinflammatory cytokines. J Nutr Biochem 23(10):1256–1263. Scholar
  29. Gilca-Blanariu GE, Diaconescu S, Ciocoiu M et al (2018) New insights into the role of trace elements in IBD. Biomed Res Int 2018:1813047. Scholar
  30. Greenberg MI, Vearrier D (2015) Metal fume fever and polymer fume fever. Clin Toxicol (Phila) 53(4):195–203. Scholar
  31. Guttek K, Wagenbrett L, Reinhold A et al (2018) Zinc aspartate suppresses proliferation and Th1/Th2/Th17 cytokine production of pre-activated human T cells in vitro. J Trace Elem Med Biol 49:86–90. doi:S0946-672X(18)30126-3 [pii]CrossRefGoogle Scholar
  32. Haase H, Ober-Blobaum JL, Engelhardt G et al (2008) Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes. J Immunol 181(9):6491–6502. doi:181/9/6491 [pii]CrossRefGoogle Scholar
  33. Haase H, Rink L (2009) Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr 29:133–152. Scholar
  34. Haase H, Rink L (2014) Zinc signals and immune function. Biofactors 40(1):27–40. Scholar
  35. Hasan R, Rink L, Haase H (2016) Chelation of free Zn(2)(+) impairs chemotaxis, phagocytosis, oxidative burst, degranulation, and cytokine production by neutrophil granulocytes. Biol Trace Elem Res 171(1):79–88. Scholar
  36. Hershfinkel M (2018) The zinc sensing receptor, ZnR/GPR39, in health and disease. Int J Mol Sci 19(2). doi:E439 [pii]
  37. Hirano T, Murakami M, Fukada T et al (2008) Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule. Adv Immunol 97:149–176. Scholar
  38. Ho Y, Samarasinghe R, Knoch ME et al (2008) Selective inhibition of mitogen-activated protein kinase phosphatases by zinc accounts for extracellular signal-regulated kinase 1/2-dependent oxidative neuronal cell death. Mol Pharmacol 74(4):1141–1151. Scholar
  39. Hojyo S, Fukada T (2016) Roles of zinc signaling in the immune system. J Immunol Res 2016:6762343. Scholar
  40. Hojyo S, Fukada T, Shimoda S et al (2011) The zinc transporter SLC39A14/ZIP14 controls G-protein coupled receptor-mediated signaling required for systemic growth. PLoS One 6(3):e18059. Scholar
  41. Hojyo S, Miyai T, Fujishiro H et al (2014) Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. Proc Natl Acad Sci U S A 111(32):11786–11791. Scholar
  42. Honscheid A, Dubben S, Rink L et al (2012) Zinc differentially regulates mitogen-activated protein kinases in human T cells. J Nutr Biochem 23(1):18–26. Scholar
  43. Jarosz M, Olbert M, Wyszogrodzka G et al (2017) Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-kappaB signaling. Inflammopharmacology 25(1):11–24. Scholar
  44. Johnsrud J, Abdallah AO, Schichman SA et al (2017) Image diagnosis: zinc-induced copper deficiency causing pancytopenia recognized on bone marrow examination. Perm J 21. doi:10.7812/TPP/16-077 [doi]
  45. Kahmann L, Uciechowski P, Warmuth S et al (2008) Zinc supplementation in the elderly reduces spontaneous inflammatory cytokine release and restores T cell functions. Rejuvenation Res 11(1):227–237. Scholar
  46. Karim T, Muhit M, Khandaker G (2017) Interventions to prevent respiratory diseases - nutrition and the developing world. Paediatr Respir Rev 22:31–37. doi:S1526-0542(16)30112-9 [pii]PubMedGoogle Scholar
  47. Kawamura T, Ogawa Y, Nakamura Y et al (2012) Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency. J Clin Invest 122(2):722–732. Scholar
  48. Kim MH, Jeong HJ (2015) Zinc oxide nanoparticles suppress LPS-induced NF-kappaB activation by inducing A20, a negative regulator of NF-kappaB, in RAW 264.7 macrophages. J Nanosci Nanotechnol 15(9):6509–6515CrossRefGoogle Scholar
  49. Kitamura H, Morikawa H, Kamon H et al (2006) Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol 7(9):971–977. doi:ni1373 [pii]CrossRefGoogle Scholar
  50. Knoell DL, Liu MJ (2010) Impact of zinc metabolism on innate immune function in the setting of sepsis. Int J Vitam Nutr Res 80(4–5):271–277. Scholar
  51. Lang C, Murgia C, Leong M et al (2007) Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. Am J Physiol Lung Cell Mol Physiol 292(2):L577–L584. doi:00280.2006 [pii]CrossRefGoogle Scholar
  52. Lee SR (2018) Critical role of zinc as either an antioxidant or a Prooxidant in cellular systems. Oxidative Med Cell Longev 2018:9156285. Scholar
  53. Li P, Xu J, Shi Y et al (2014) Association between zinc intake and risk of digestive tract cancers: a systematic review and meta-analysis. Clin Nutr 33(3):415–420. Scholar
  54. Liu MJ, Bao S, Galvez-Peralta M et al (2013) ZIP8 regulates host defense through zinc-mediated inhibition of NF-kappaB. Cell Rep 3(2):386–400. Scholar
  55. Liu T, Zhang L, Joo D et al (2017) NF-kappaB signaling in inflammation. Signal Transduct Target Ther 2. Epub 2017 Jul 14. doi:17023 [pii]
  56. Lu H, Xin Y, Tang Y et al (2012) Zinc suppressed the airway inflammation in asthmatic rats: effects of zinc on generation of eotaxin, MCP-1, IL-8, IL-4, and IFN-gamma. Biol Trace Elem Res 150(1–3):314–321. Scholar
  57. Maares M, Haase H (2016) Zinc and immunity: an essential interrelation. Arch Biochem Biophys 611:58–65. doi:S0003-9861(16)30074-1 [pii]CrossRefGoogle Scholar
  58. Malik A, Taneja DK, Devasenapathy N et al (2014) Zinc supplementation for prevention of acute respiratory infections in infants: a randomized controlled trial. Indian Pediatr 51(10):780–784CrossRefGoogle Scholar
  59. Maret W (2017) Zinc in cellular regulation: the nature and significance of “zinc signals”. Int J Mol Sci 18(11). doi:E2285 [pii]
  60. Marreiro DD, Cruz KJ, Morais JB et al (2017) Zinc and oxidative stress: current mechanisms. Antioxidants (Basel) 6(2): doi:E24 [pii]
  61. Mayer LS, Uciechowski P, Meyer S et al (2014) Differential impact of zinc deficiency on phagocytosis, oxidative burst, and production of pro-inflammatory cytokines by human monocytes. Metallomics 6(7):1288–1295. Scholar
  62. Maywald M, Rink L (2015) Zinc homeostasis and immunosenescence. J Trace Elem Med Biol 29:24–30. Scholar
  63. Maywald M, Rink L (2017) Zinc supplementation induces CD4(+)CD25(+)Foxp3(+) antigen-specific regulatory T cells and suppresses IFN-gamma production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. Eur J Nutr 56(5):1859–1869. Scholar
  64. Maywald M, Wessels I, Rink L (2017) Zinc signals and immunity. Int J Mol Sci 18(10): doi:E2222 [pii]
  65. Meksawan K, Sermsri U, Chanvorachote P (2014) Zinc supplementation improves anticancer activity of monocytes in type-2 diabetic patients with metabolic syndrome. Anticancer Res 34(1):295–299. doi:34/1/295 [pii]PubMedGoogle Scholar
  66. Meydani SN, Barnett JB, Dallal GE et al (2007) Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr 86(4):1167–1173. doi:86/4/1167 [pii]CrossRefGoogle Scholar
  67. Miyai T, Hojyo S, Ikawa T et al (2014) Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development. Proc Natl Acad Sci U S A 111(32):11780–11785. Scholar
  68. Morgan CI, Ledford JR, Zhou P et al (2011) Zinc supplementation alters airway inflammation and airway hyperresponsiveness to a common allergen. J Inflamm (Lond) 8:36–9255-8-36. Scholar
  69. Morris DR, Levenson CW (2012) Ion channels and zinc: mechanisms of neurotoxicity and neurodegeneration. J Toxicol 2012:785647. Scholar
  70. Muller A, Kleinau G, Piechowski CL et al (2013) G-protein coupled receptor 83 (GPR83) signaling determined by constitutive and zinc(II)-induced activity. PLoS One 8(1):e53347. Scholar
  71. Murakami M, Hirano T (2008) Intracellular zinc homeostasis and zinc signaling. Cancer Sci 99(8):1515–1522. Scholar
  72. Myers S, Shastri MD, Adulcikas J et al (2017) Zinc and gastrointestinal disorders: a role for the zinc transporters zips and ZnTs. Curr Pharm Des 23(16):2328–2332. Scholar
  73. Nikolich-Zugich J (2014) Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol 193(6):2622–2629. Scholar
  74. Nimmanon T, Ziliotto S, Morris S et al (2017) Phosphorylation of zinc channel ZIP7 drives MAPK, PI3K and mTOR growth and proliferation signalling. Metallomics 9(5):471–481. Scholar
  75. Nishida K, Hasegawa A, Nakae S et al (2009) Zinc transporter Znt5/Slc30a5 is required for the mast cell-mediated delayed-type allergic reaction but not the immediate-type reaction. J Exp Med 206(6):1351–1364. Scholar
  76. Nishida K, Uchida R (2018) Role of zinc signaling in the regulation of mast cell-, basophil-, and T cell-mediated allergic responses. J Immunol Res 2018:5749120. Scholar
  77. Nuttall JR, Oteiza PI (2012) Zinc and the ERK kinases in the developing brain. Neurotox Res 21(1):128–141. Scholar
  78. Olechnowicz J, Tinkov A, Skalny A et al (2018) Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci 68(1):19–31. Scholar
  79. Ollig J, Kloubert V, Taylor KM et al (2019) B cell activation and proliferation increase intracellular zinc levels. J Nutr Biochem 64:72–79. doi:S0955-2863(18)30724-1 [pii]CrossRefGoogle Scholar
  80. Paoletti P, Vergnano AM, Barbour B et al (2009) Zinc at glutamatergic synapses. Neuroscience 158(1):126–136. Scholar
  81. Plum LM, Rink L, Haase H (2010) The essential toxin: impact of zinc on human health. Int J Environ Res Public Health 7(4):1342–1365. Scholar
  82. Pongkorpsakol P, Buasakdi C, Chantivas T et al (2019) An agonist of a zinc-sensing receptor GPR39 enhances tight junction assembly in intestinal epithelial cells via an AMPK-dependent mechanism. Eur J Pharmacol 842:306–313. doi:S0014-2999(18)30623-X [pii]CrossRefGoogle Scholar
  83. Prasad AS (2012) Discovery of human zinc deficiency: 50 years later. J Trace Elem Med Biol 26(2–3):66–69. Scholar
  84. Prasad AS, Bao B, Beck FW et al (2011) Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-kappaB. Nutrition 27(7–8):816–823. Scholar
  85. Pyle CJ, Akhter S, Bao S et al (2017) Zinc modulates endotoxin-induced human macrophage inflammation through ZIP8 induction and C/EBPbeta inhibition. PLoS One 12(1):e0169531. Scholar
  86. Rao G, Rowland K (2011) PURLs: zinc for the common cold – not if, but when. J Fam Pract 60(11):669–671. jfp_6011g [pii]PubMedPubMedCentralGoogle Scholar
  87. Rerksuppaphol S, Rerksuppaphol L (2016) Zinc supplementation in children with asthma exacerbation. Pediatr Rep 8(4):6685. Scholar
  88. Rosenkranz E, Hilgers RD, Uciechowski P et al (2017) Zinc enhances the number of regulatory T cells in allergen-stimulated cells from atopic subjects. Eur J Nutr 56(2):557–567. Scholar
  89. Roth DE, Richard SA, Black RE (2010) Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries: meta-analysis and meta-regression of randomized trials. Int J Epidemiol 39(3):795–808. Scholar
  90. Salam N, Rane S, Das R et al (2013) T cell ageing: effects of age on development, survival & function. Indian J Med Res 138(5):595–608. doi:IndianJMedRes_2013_138_5_595_124628 [pii]PubMedPubMedCentralGoogle Scholar
  91. Salazar G, Huang J, Feresin RG et al (2017) Zinc regulates Nox1 expression through a NF-kappaB and mitochondrial ROS dependent mechanism to induce senescence of vascular smooth muscle cells. Free Radic Biol Med 108:225–235. S0891-5849(17)30186-7 [pii]CrossRefGoogle Scholar
  92. Sapkota M, Knoell DL (2018) Essential role of zinc and zinc transporters in myeloid cell function and host defense against infection. J Immunol Res 2018:4315140. Scholar
  93. Sato S, Huang XP, Kroeze WK et al (2016) Discovery and characterization of novel GPR39 agonists allosterically modulated by zinc. Mol Pharmacol 90(6):726–737. doi:mol.116.106112 [pii]CrossRefGoogle Scholar
  94. Sayadi A, Nguyen AT, Bard FA et al (2013) Zip14 expression induced by lipopolysaccharides in macrophages attenuates inflammatory response. Inflamm Res 62(2):133–143. Scholar
  95. Science M, Johnstone J, Roth DE et al (2012) Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 184(10):E551–E561. Scholar
  96. Sensi SL, Granzotto A, Siotto M et al (2018) Copper and zinc dysregulation in Alzheimer’s disease. Trends Pharmacol Sci 39(12):1049–1063. doi:S0165-6147(18)30179-2 [pii]CrossRefGoogle Scholar
  97. Sensi SL, Paoletti P, Koh JY et al (2011) The neurophysiology and pathology of brain zinc. J Neurosci 31(45):16076–16085. Scholar
  98. Shao YX, Lei Z, Wolf PG et al (2017) Zinc supplementation, via GPR39, upregulates PKCzeta to protect intestinal barrier integrity in Caco-2 cells challenged by Salmonella enterica Serovar typhimurium. J Nutr 147(7):1282–1289. Scholar
  99. Shumilina E, Xuan NT, Schmid E et al (2010) Zinc induced apoptotic death of mouse dendritic cells. Apoptosis 15(10):1177–1186. Scholar
  100. Skrovanek S, DiGuilio K, Bailey R et al (2014) Zinc and gastrointestinal disease. World J Gastrointest Pathophysiol 5(4):496–513. Scholar
  101. Someya Y, Tanihata J, Sato S et al (2009) Zinc-deficiency induced changes in the distribution of rat white blood cells. J Nutr Sci Vitaminol (Tokyo) 55(2):162–169. doi:JST.JSTAGE/jnsv/55.162 [pii]CrossRefGoogle Scholar
  102. Souffriau J, Libert C (2018) Mechanistic insights into the protective impact of zinc on sepsis. Cytokine Growth Factor Rev 39:92–101. doi:S1359-6101(17)30188-0 [pii]CrossRefGoogle Scholar
  103. Stafford SL, Bokil NJ, Achard ME et al (2013) Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper. Biosci Rep 33(4).
  104. Subramanian Vignesh K, Deepe GS Jr (2016) Immunological orchestration of zinc homeostasis: the battle between host mechanisms and pathogen defenses. Arch Biochem Biophys 611:66–78. doi:S0003-9861(16)30039-X [pii]CrossRefGoogle Scholar
  105. Subramanian Vignesh K, Landero Figueroa JA, Porollo A et al (2016) IL-4 induces Metallothionein 3- and SLC30A4-dependent increase in intracellular Zn(2+) that promotes pathogen persistence in macrophages. Cell Rep 16(12):3232–3246. doi:S2211-1247(16)31138-X [pii]CrossRefGoogle Scholar
  106. Sunuwar L, Gilad D, Hershfinkel M (2017) The zinc sensing receptor, ZnR/GPR39, in health and disease. Front Biosci (Landmark Ed) 22:1469–1492. doi:4554 [pii]CrossRefGoogle Scholar
  107. Supasai S, Aimo L, Adamo AM et al (2017) Zinc deficiency affects the STAT1/3 signaling pathways in part through redox-mediated mechanisms. Redox Biol 11:469–481. doi:S2213-2317(16)30353-6 [pii]CrossRefGoogle Scholar
  108. Szewczyk B (2013) Zinc homeostasis and neurodegenerative disorders. Front Aging Neurosci 5:33. Scholar
  109. Taylor KM, Hiscox S, Nicholson RI et al (2012) Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. Sci Signal 5(210):ra11. Scholar
  110. Toth K (2011) Zinc in neurotransmission. Annu Rev Nutr 31:139–153. Scholar
  111. Triner D, Castillo C, Hakim JB et al (2018) Myc-associated zinc finger protein regulates the proinflammatory response in colitis and colon cancer via STAT3 Signaling. Mol Cell Biol 38(22): Print 2018 Nov 15. doi:e00386–18 [pii]
  112. Uzzo RG, Crispen PL, Golovine K et al (2006) Diverse effects of zinc on NF-kappaB and AP-1 transcription factors: implications for prostate cancer progression. Carcinogenesis 27(10):1980–1990. doi:bgl034 [pii]CrossRefGoogle Scholar
  113. Villarino AV, Kanno Y, Ferdinand JR et al (2015) Mechanisms of Jak/STAT signaling in immunity and disease. J Immunol 194(1):21–27. Scholar
  114. Wessells KR, Brown KH (2012) Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One 7(11):e50568. Scholar
  115. Willis MS, Monaghan SA, Miller ML et al (2005) Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 123(1):125–131CrossRefGoogle Scholar
  116. Wong CP, Magnusson KR, Ho E (2013) Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation. J Nutr Biochem 24(1):353–359. Scholar
  117. Wong CP, Rinaldi NA, Ho E (2015) Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation. Mol Nutr Food Res 59(5):991–999. Scholar
  118. Xia S, Zhang X, Zheng S et al (2016) An update on Inflamm-aging: mechanisms, prevention, and treatment. J Immunol Res 2016:8426874. Scholar
  119. Yamasaki S, Sakata-Sogawa K, Hasegawa A et al (2007) Zinc is a novel intracellular second messenger. J Cell Biol 177(4):637–645. doi:jcb.200702081 [pii]CrossRefGoogle Scholar
  120. Yan YW, Fan J, Bai SL et al (2016) Zinc prevents abdominal aortic aneurysm formation by induction of A20-mediated suppression of NF-kappaB pathway. PLoS One 11(2):e0148536. Scholar
  121. Yasuda H, Tsutsui T (2016) Infants and elderlies are susceptible to zinc deficiency. Sci Rep 6:21850. Scholar
  122. Yu M, Lee WW, Tomar D et al (2011) Regulation of T cell receptor signaling by activation-induced zinc influx. J Exp Med 208(4):775–785. Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.College of Pharmacy, Pharmacy Practice and ScienceUniversity of Nebraska Medical CenterOmahaUSA

Personalised recommendations