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Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38 MAPK/NF-κB-IL-6/TNF-α positive-feedback circuit.
PLoS One. 2014; 9(4):e93837.Plos

Abstract

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.

Authors+Show Affiliations

Emergency department, the 2nd affiliated hospital of Chongqing Medical University, Chongqing, China.Department of Pharmacy, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24714343

Citation

Wang, Xiaolong, et al. "Paraquat-induced Reactive Oxygen Species Inhibit Neutrophil Apoptosis Via a P38 MAPK/NF-κB-IL-6/TNF-α Positive-feedback Circuit." PloS One, vol. 9, no. 4, 2014, pp. e93837.
Wang X, Luo F, Zhao H. Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38 MAPK/NF-κB-IL-6/TNF-α positive-feedback circuit. PLoS ONE. 2014;9(4):e93837.
Wang, X., Luo, F., & Zhao, H. (2014). Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38 MAPK/NF-κB-IL-6/TNF-α positive-feedback circuit. PloS One, 9(4), e93837. https://doi.org/10.1371/journal.pone.0093837
Wang X, Luo F, Zhao H. Paraquat-induced Reactive Oxygen Species Inhibit Neutrophil Apoptosis Via a P38 MAPK/NF-κB-IL-6/TNF-α Positive-feedback Circuit. PLoS ONE. 2014;9(4):e93837. PubMed PMID: 24714343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38 MAPK/NF-κB-IL-6/TNF-α positive-feedback circuit. AU - Wang,Xiaolong, AU - Luo,Fuling, AU - Zhao,Hengguang, Y1 - 2014/04/08/ PY - 2014/01/04/received PY - 2014/03/06/accepted PY - 2014/4/10/entrez PY - 2014/4/10/pubmed PY - 2015/1/7/medline SP - e93837 EP - e93837 JF - PloS one JO - PLoS ONE VL - 9 IS - 4 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24714343/Paraquat_induced_reactive_oxygen_species_inhibit_neutrophil_apoptosis_via_a_p38_MAPK/NF_κB_IL_6/TNF_α_positive_feedback_circuit_ L2 - http://dx.plos.org/10.1371/journal.pone.0093837 DB - PRIME DP - Unbound Medicine ER -