The Increase in IL-1β in the Early Stage of Heatstroke Might Be Caused by Splenic Lymphocyte Pyroptosis Induced by mtROS-Mediated Activation of the NLRP3 Inflammasome
Authors: Zhen Luo
Genlin He
He Tang
Jun Liu
Ping Li
Ju Yang
Tingting Shen
Yulong Tan
Xue Luo
Yuan Wang
Xuesen Yang
Gong Wang
Xiaoliang Zhang
Journal: Frontiers in Immunology (2019)
Discipline: IMMUNOLOGY
Keywords: NLRP3 inflammasome; heatstroke; mtROS; pyroptosis; splenic lymphocytes.
Affiliations: Department of Tropical Medicine, College of Military Preventive Medicine, Army Medical University, Chongqing, China., Department of Neurology, Xinqiao Hospital, Army Medical University, Chongqing, China.

Abstract:  Interleukin-1β (IL-1β) is important for the pathological process of heatstroke (HS), although little is known regarding the main source of the IL-1β produced during the early stage of HS. In this study, heat stress led splenic lymphocytes to death with generation of inflammatory cytokines. The same phenomenon also occurs in animal models of heatshock. We observed that the death of splenic lymphocytes was identified to be pyroptosis. In addition, splenic lymphocyte pyroptosis can be induced by hyperpyrexia in a time- and temperature-dependent manner with NLR pyrin domain containing 3 (NLRP3) inflammasome activation. An NLRP3 inhibitor (MCC950) and a caspase-1 inhibitor (ac-YVAD-cmk) were used to confirm the role of the NLRP3/caspase-1 pathway in pyroptosis. With heat stress, levels of mitochondrial reactive oxygen species (mtROS) in splenic lymphocytes would significantly increase. Accordingly, the use of mtROS scavenger (Mito-TEMPO) could reduce the occurrence of pyroptosis and the activation of the NLRP3 inflammasome in vitro. In animal models of heatshock, Mito-TEMPO can inhibit activation of the NLRP3/caspase-1 pathway. Taken together, our data suggest that activation of the NLRP3 inflammasome mediates hyperpyrexia-induced pyroptosis in splenic lymphocytes. Perhaps one of the important initiators of pyroptosis is mtROS. Our data have elucidated a new molecular mechanism of IL-1β overexpression in the early stage of HS, providing a new strategy for IL-1β-targeted therapy in future clinical treatments for HS. 

Retracted: Yes

PubPeer comments:
 2020 retraction. https: www.frontiersin.org articles 10.3389 fimmu.2020.01863 full Frontiers Editorial Office* A Retraction of the Original Research Article The Increase in IL-1u03b2 in the Early Stage of Heatstroke Might Be Caused by Splenic Lymphocyte Pyroptosis Induced by mtROS-Mediated Activation of the NLRP3 Inflammasome by Wang, G., Shen, T., Li, P., Luo, Z., Tan, Y., He, G., et al. (2019). Front. Immunol. 10:2862. doi: 10.3389 fimmu.2019.02862 The journal retracts the 11 December 2019 article cited above. Following the publication of the article, concerns regarding the Figures were addressed to the journal and its Editorial Board. It was confirmed that FACS plots in Figures 4C, 4D, 5, and 9 had been duplicated. Confronted with this concern, the corresponding author confirmed that inappropriate methods had been used to obtain the relevant data and that the images had been manipulated. As a result of this, the scientific conclusions of the manuscript may be unreliable. The article is therefore being retracted. The authors concur with the retraction and sincerely regret any inconvenience this may have caused to the reviewers, editors, and readers of Frontiers in Immunology. ,