HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice

Abstract Paraquat is a poisoning herbicide that primarily targets lung, leading to severe acute lung injury characterized by extensive neutrophil infiltration. However, the mechanisms underlying the neutrophil infiltration is not clear. In this study, we demonstrated the significance of the signalin...

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Autores principales:	Bailing Yan, Feng Chen, Lijun Xu, Jihong Xing, Xuefu Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06174d3f9d0748a3bee5c320110d067a
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spelling	oai:doaj.org-article:06174d3f9d0748a3bee5c320110d067a2021-12-02T16:07:01ZHMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice10.1038/s41598-017-00721-82045-2322https://doaj.org/article/06174d3f9d0748a3bee5c320110d067a2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00721-8https://doaj.org/toc/2045-2322Abstract Paraquat is a poisoning herbicide that primarily targets lung, leading to severe acute lung injury characterized by extensive neutrophil infiltration. However, the mechanisms underlying the neutrophil infiltration is not clear. In this study, we demonstrated the significance of the signaling cascade from high-mobility group box 1 (HMGB1), to Toll-like receptor 4 (TLR4), interleukin-23 (IL-23), and lastly to IL-17A during the paraquat-induced neutrophil infiltration and the subsequent lung injury in mice. Paraquat challenge significantly elevated serum levels of IL-17A and IL-23, the percentage of IL-17A-producing γδT cells in the lung, and the level of HMGB1 in bronchoalveolar lavage fluid. Reducing IL-17A production using an anti-γδT antibody, targeting IL-23 with the neutralizing antibody against IL-23p19, and blocking HMGB1 signaling by using glycyrrhizin or TLR4−/− mice all dramatically inhibited the infiltration of neutrophils and attenuated lung injury. These novel findings not only reveal the critical role of HMGB1-TLR4-IL-23-IL-17A axis in the pathogenesis of paraquat-induced acute lung injury, but also provide promising therapeutic targets for treating paraquat poisoning.Bailing YanFeng ChenLijun XuJihong XingXuefu WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bailing Yan Feng Chen Lijun Xu Jihong Xing Xuefu Wang HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
description	Abstract Paraquat is a poisoning herbicide that primarily targets lung, leading to severe acute lung injury characterized by extensive neutrophil infiltration. However, the mechanisms underlying the neutrophil infiltration is not clear. In this study, we demonstrated the significance of the signaling cascade from high-mobility group box 1 (HMGB1), to Toll-like receptor 4 (TLR4), interleukin-23 (IL-23), and lastly to IL-17A during the paraquat-induced neutrophil infiltration and the subsequent lung injury in mice. Paraquat challenge significantly elevated serum levels of IL-17A and IL-23, the percentage of IL-17A-producing γδT cells in the lung, and the level of HMGB1 in bronchoalveolar lavage fluid. Reducing IL-17A production using an anti-γδT antibody, targeting IL-23 with the neutralizing antibody against IL-23p19, and blocking HMGB1 signaling by using glycyrrhizin or TLR4−/− mice all dramatically inhibited the infiltration of neutrophils and attenuated lung injury. These novel findings not only reveal the critical role of HMGB1-TLR4-IL-23-IL-17A axis in the pathogenesis of paraquat-induced acute lung injury, but also provide promising therapeutic targets for treating paraquat poisoning.
format	article
author	Bailing Yan Feng Chen Lijun Xu Jihong Xing Xuefu Wang
author_facet	Bailing Yan Feng Chen Lijun Xu Jihong Xing Xuefu Wang
author_sort	Bailing Yan
title	HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
title_short	HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
title_full	HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
title_fullStr	HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
title_full_unstemmed	HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
title_sort	hmgb1-tlr4-il23-il17a axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/06174d3f9d0748a3bee5c320110d067a
work_keys_str_mv	AT bailingyan hmgb1tlr4il23il17aaxispromotesparaquatinducedacutelunginjurybymediatingneutrophilinfiltrationinmice AT fengchen hmgb1tlr4il23il17aaxispromotesparaquatinducedacutelunginjurybymediatingneutrophilinfiltrationinmice AT lijunxu hmgb1tlr4il23il17aaxispromotesparaquatinducedacutelunginjurybymediatingneutrophilinfiltrationinmice AT jihongxing hmgb1tlr4il23il17aaxispromotesparaquatinducedacutelunginjurybymediatingneutrophilinfiltrationinmice AT xuefuwang hmgb1tlr4il23il17aaxispromotesparaquatinducedacutelunginjurybymediatingneutrophilinfiltrationinmice
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HMGB1-TLR4-IL23-IL17A axis promotes paraquat-induced acute lung injury by mediating neutrophil infiltration in mice

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