Nuclear Factor κB1/RelA Mediates Inflammation in Human Lung Epithelial Cells at Atmospheric Oxygen Levels

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-B1/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-B1/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 H2O2 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. (c) 2015 Wiley Periodicals, Inc.