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Aberrant cytokine secretion and zinc uptake in chronic cadmium‐exposed lung epithelial cells
Author(s) -
Xu YanMing,
Gao YangMin,
Wu DanDan,
Yu FeiYuan,
Zang ZhongSheng,
Yang Lei,
Yao Yue,
Cai NaLi,
Zhou Yuan,
Chiu JenFu,
Ching YickPang,
Lau Andy T. Y.
Publication year - 2017
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201600059
Subject(s) - cytokine , microbiology and biotechnology , secretion , angiogenesis , biology , homeostasis , cytotoxicity , chemistry , immunology , cancer research , endocrinology , in vitro , biochemistry
Purpose Our previous results showed that cadmium (Cd)‐adapted lung epithelial cells (LECs) developed resistance to apoptosis due to non‐responsiveness of the c‐Jun N‐terminal kinase pathway and augmented expression of cytokeratin 8. Since cellular Cd entry is a prerequisite in order for Cd to elicit its cytotoxicity, therefore, we wonder if there are differential metal ion transport ability and also other phenotypic changes that occurred in these Cd‐resistant LECs. Experimental design and results Here, we explored further and found that the zinc (Zn) importer Zip8 was stably abolished in these cells along with a marked decrease of Cd and Zn accumulation. Moreover, by cell migration assays and cytokine antibody array analysis, we found that Cd‐adapted cells exhibit enhanced migratory ability possibly due to elevated secretions of vascular endothelial growth factor and macrophage inflammatory protein‐3 alpha (MIP‐3α). Conclusion and clinical relevance Taken together, our results show that during chronic Cd exposure, lung cells antagonize excessive cellular Cd‐influx by abolishing Zip8 expression to reduce Cd‐toxicity; however, this also renders cells with a diminished Zn uptake. The imbalance of Zn homeostasis and elevation of angiogenic and epithelial–mesenchymal transition‐promoting cytokines in Cd‐adapted cells might thus likely promote Zn deficiency, angiogenesis, and cell invasion.