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Aging of the antioxidant/inflammatory axis in human lung epithelial cells in vitro mimics aging in animal studies
Author(s) -
Zhou Lulu,
Forman Henry Jay,
Zhang Hongqiao
Publication year - 2016
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.30.1_supplement.1296.3
Subject(s) - gclc , gclm , sulforaphane , lipopolysaccharide , inflammation , antioxidant , gene expression , nf κb , in vitro , microbiology and biotechnology , tumor necrosis factor alpha , a549 cell , proinflammatory cytokine , gene , biology , chemistry , immunology , cancer research , downregulation and upregulation , biochemistry
The balance of cellular antioxidant/inflammation shifts with aging, which results from increased pro‐inflammatory cytokines and inhibition of the Nrf2 pathway. Human small airway epithelial (SAE) cells were stimulated with lipopolysaccharide at 5 μg/ml and sulforaphane at 2 μM for 12 hours in vitro. The mRNA of cell inflammatory (NF‐κB‐dependent) and Nrf2 mediated production of antioxidant (phase II) genes were analyzed at early and late passage level of SAE. It was discovered that with the treatment of sulforaphane, phase II gene expression decreases as cell passage increases. GCLC and GCLM genes were down regulated, which may result from decreased capacity of cells to respond to electrophiles. However, upon treatment with lipopolysaccharide, NF‐kB dependent genes IL‐1 and TNF‐a were up regulated in company with inhibited phase II gene expression. The up‐regulation of pro‐inflammatory gene expression together with inhibition of Nrf2 mediated genes suggests that aging human epithelial cells gradually lose the ability to induce antioxidant defense, permitting a greater NF‐kB‐regulated increase in inflammatory cytokines. This mimics what has been observed in several previously reported studies of animal organs. Support or Funding Information Supported by NIH grant ES023864