Open AccessParaquat-Induced Reactive Oxygen Species Inhibit Neutrophil Apoptosis via a p38 MAPK/NF-κB–IL-6/TNF-α Positive-Feedback Circuit
Author(s) -
Xiaolong Wang,
Fang Luo,
Hengguang Zhao
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0093837
Subject(s) - reactive oxygen species , proinflammatory cytokine , paraquat , p38 mitogen activated protein kinases , tumor necrosis factor alpha , microbiology and biotechnology , apoptosis , mapk/erk pathway , signal transduction , protein kinase b , chemistry , biology , inflammation , cancer research , immunology , biochemistry
Paraquat (PQ), a widely used herbicide and potent reactive oxygen species (ROS) inducer, can injure multiple tissues and organs, especially the lung. However, the underlying mechanism is still poorly understood. According to previous reports, neutrophil aggregation and excessive ROS production might play pivotal pathogenetic roles. In the present study, we found that PQ could prolong neutrophil lifespan and induce ROS generation in a concentration-independent manner. Activated nuclear factor-κB (NF-κB), p38 mitogen-activated kinase (p38 MAPK), and myeloid cell leukemia sequence 1 (Mcl-1) but not Akt signaling pathways were involved in this process, as well as increasing levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β. Furthermore, the proinflammatory mediators IL-6 and TNF-α could in turn promote ROS generation, creating a vicious cycle. The existence of such a feedback loop is supported by our finding that neutrophil apoptosis is attenuated by PQ in a concentration-independent manner and could partially explain the clinical dilemma why oxygen therapy will exacerbate PQ induced tissue injury.