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Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases
Authors:Masanobu Suzuki  Takayoshi Suzuki  Masashi Watanabe  Shigetsugu Hatakeyama  Shogo Kimura  Akira Nakazono  Aya Honma  Yuji Nakamaru  Sarah Vreugde  Akihiro Homma
Institution:1. Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan;2. Department of Surgery–Otorhinolaryngology Head and Neck Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Australia;3. Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
Abstract:Zinc is an essential micronutrient in human body and a vital cofactor for the function of numerous proteins encoded by the human genome. Zinc has a critical role in maintaining many biochemical and physiological processes at the molecular, cellular, and multiple organ and systemic levels. The alteration of zinc homeostasis causes dysfunction of many organs and systems.In the immune system, zinc regulates the differentiation, proliferation and function of inflammatory cells, including T cells, eosinophils, and B cells, by modifying several signaling pathways such as NFκB signaling pathways and TCR signals. An adequate zinc level is essential for proper immune responses and decreased zinc levels were reported in many allergic inflammatory diseases, including atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. Decreased zinc levels often enhance inflammatory activation. On the other hand, the inflammatory conditions alter the intracellular homeostasis of zinc, often decreasing zinc levels. These findings implied that there could be a vicious cycle between zinc deficiency and inflammatory conditions.In this review, we present recent evidence on the involvement of zinc in atopic dermatitis, bronchial asthma, and chronic rhinosinusitis, with insights into the involvement of zinc in the underlying molecular and cellular mechanisms related to these allergic inflammatory diseases.
Keywords:Atopic dermatitis  Bronchial asthma  Chronic rhinosinusitis  Nasal polyps  Zinquin  AD"}  {"#name":"keyword"  "$":{"id":"kwrd0040"}  "$$":[{"#name":"text"  "_":"atopic dermatitis  BA"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"bronchial asthma  BCR"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"B cell receptor  CF"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"cystic fibrosis  CRS"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"chronic rhinosinusitis  CRSsNP"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"chronic rhinosinusitis without nasal polyps  CRSwNP"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "_":"chronic rhinosinusitis with nasal polyps  ECM"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "_":"extracellular matrix  FLG"}  {"#name":"keyword"  "$":{"id":"kwrd0120"}  "$$":[{"#name":"text"  "_":"Filaggrin  IKK"}  {"#name":"keyword"  "$":{"id":"kwrd0130"}  "$$":[{"#name":"text"  "_":"IκB kinase  MMPs"}  {"#name":"keyword"  "$":{"id":"kwrd0140"}  "$$":[{"#name":"text"  "_":"matrix-metalloproteinases  MTs"}  {"#name":"keyword"  "$":{"id":"kwrd0150"}  "$$":[{"#name":"text"  "_":"metallothioneins  PKA"}  {"#name":"keyword"  "$":{"id":"kwrd0160"}  "$$":[{"#name":"text"  "_":"protein kinase A  PKC"}  {"#name":"keyword"  "$":{"id":"kwrd0170"}  "$$":[{"#name":"text"  "_":"protein kinase C  PKG"}  {"#name":"keyword"  "$":{"id":"kwrd0180"}  "$$":[{"#name":"text"  "_":"protein kinase G  PP2A"}  {"#name":"keyword"  "$":{"id":"kwrd0190"}  "$$":[{"#name":"text"  "_":"protein phosphatase 2A  PTK"}  {"#name":"keyword"  "$":{"id":"kwrd0200"}  "$$":[{"#name":"text"  "_":"protein tyrosine kinase  PTP"}  {"#name":"keyword"  "$":{"id":"kwrd0210"}  "$$":[{"#name":"text"  "_":"protein tyrosine phosphatase  SHP-1"}  {"#name":"keyword"  "$":{"id":"kwrd0220"}  "$$":[{"#name":"text"  "_":"Src homology 2 domain-containing protein tyrosine phosphatase 1  TCR"}  {"#name":"keyword"  "$":{"id":"kwrd0230"}  "$$":[{"#name":"text"  "_":"T cell receptor (TCR  TEWL"}  {"#name":"keyword"  "$":{"id":"kwrd0240"}  "$$":[{"#name":"text"  "_":"transepidermal water loss (TEWL)  TNFR"}  {"#name":"keyword"  "$":{"id":"kwrd0250"}  "$$":[{"#name":"text"  "_":"TNFα receptor  TRIM"}  {"#name":"keyword"  "$":{"id":"kwrd0260"}  "$$":[{"#name":"text"  "_":"tripartite motif  ZIP"}  {"#name":"keyword"  "$":{"id":"kwrd0270"}  "$$":[{"#name":"text"  "_":"Zrt-/Irt-like proteins  ZnT"}  {"#name":"keyword"  "$":{"id":"kwrd0280"}  "$$":[{"#name":"text"  "_":"Zinc transporters  β-TrCP"}  {"#name":"keyword"  "$":{"id":"kwrd0290"}  "$$":[{"#name":"text"  "_":"β-transducin repeat-containing protein
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