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Pro‐inflammatory cytokines dysregulate mammary gland zinc homeostasis
Author(s) -
Hennigar Stephen R,
Kelleher Shan L
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.228.3
Subject(s) - homeostasis , inflammation , metallothionein , endocrinology , biology , apoptosis , proinflammatory cytokine , tumor necrosis factor alpha , mammary gland , medicine , microbiology and biotechnology , intracellular , signal transduction , glucose homeostasis , chemistry , zinc , immunology , biochemistry , cancer , insulin , insulin resistance , breast cancer , organic chemistry
Inflammatory conditions such as obesity and breast cancer are increasingly prevalent and are associated with impairments in mammary gland function. Each is characterized by increased circulating pro‐inflammatory cytokines (PIC), such as TNFα and IL6. Zinc (Zn) is an essential nutrient required for cell proliferation and differentiation, as well as signal transduction and apoptosis. Cytokines have been shown to mediate Zn metabolism in certain cell types, such as pancreatic β‐cells and T cells. The objective of this study was to determine if PIC modulate Zn homeostasis in mammary epithelial cells. HC11 cells treated with TNFα or IL6 (15 ng/mL) reduced metallothionein mRNA expression by 94 and 53‐fold, respectively, indicating a decrease in cytoplasmic Zn. Fluozin‐3 staining revealed vesicularized Zn pools in untreated cells, which were redistributed to large intracellular vesicles following treatment with PIC. Furthermore, cells treated with TNFα or IL6 secreted less Zn (46 and 38%, respectively) compared with untreated cells. These data indicate that PIC may relocate cellular Zn pools in mammary epithelial cells, which may lead to sequestration and decreased Zn export. Given the widespread prevalence of pro‐inflammatory conditions and the essentiality of Zn, altered Zn homeostasis during periods of inflammation may result in decreased Zn transfer to the nursing infant, leading to adverse health outcomes. Grant Funding Source: NIH HD058614