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Nuclear Factor κB1/RelA Mediates Inflammation in Human Lung Epithelial Cells at Atmospheric Oxygen Levels
Author(s) -
Jagannathan Lakshmanan,
Jose Cynthia C.,
Arita Adriana,
Kluz Thomas,
Sun Hong,
Zhang Xiaoru,
Yao Yixin,
Kartashov Andrey V.,
Barski Artem,
Costa Max,
Cuddapah Suresh
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25262
Subject(s) - downregulation and upregulation , inflammation , microbiology and biotechnology , cell culture , gene knockdown , senescence , biology , immortalised cell line , proinflammatory cytokine , oxidative stress , cell , a549 cell , immunology , cancer research , gene , biochemistry , genetics
Oxygen levels range from 2% to 9% in vivo. Atmospheric O 2 levels (21%) are known to induce cell proliferation defects and cellular senescence in primary cell cultures. However, the mechanistic basis of the deleterious effects of higher O 2 levels is not fully understood. On the other hand, immortalized cells including cancer cell lines, which evade cellular senescence are normally cultured at 21% O 2 and the effects of higher O 2 on these cells are understudied. Here, we addressed this problem by culturing immortalized human bronchial epithelial (BEAS‐2B) cells at ambient atmospheric, 21% O 2 and lower, 10% O 2 . Our results show increased inflammatory response at 21% O 2 but not at 10% O 2 . We found higher RelA binding at the NF‐κB1/RelA target gene promoters as well as upregulation of several pro‐inflammatory cytokines in cells cultured at 21% O 2 . RelA knockdown prevented the upregulation of the pro‐inflammatory cytokines at 21% O 2 , suggesting NF‐κB1/RelA as a major mediator of inflammatory response in cells cultured at 21% O 2 . Interestingly, unlike the 21% O 2 cultured cells, exposure of 10% O 2 cultured cells to H 2 O 2 did not elicit inflammatory response, suggesting increased ability to tolerate oxidative stress in cells cultured at lower O 2 levels. J. Cell. Physiol. 231: 1611–1620, 2016. © 2015 Wiley Periodicals, Inc.