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HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways
High mobility group box 1 (HMGB1), a crucial proinflammatory cytokine, was reported to activate the absent in melanoma 2 (AIM2) inflammasome, which are both essential in acute lung injury (ALI). However, their interaction mechanism has remained elusive. Macrophages are known to express the AIM2 infl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889921/ https://www.ncbi.nlm.nih.gov/pubmed/31746367 http://dx.doi.org/10.3892/ijmm.2019.4402 |
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author | Wang, Jing Li, Ruiting Peng, Zhiyong Hu, Bo Rao, Xin Li, Jianguo |
author_facet | Wang, Jing Li, Ruiting Peng, Zhiyong Hu, Bo Rao, Xin Li, Jianguo |
author_sort | Wang, Jing |
collection | PubMed |
description | High mobility group box 1 (HMGB1), a crucial proinflammatory cytokine, was reported to activate the absent in melanoma 2 (AIM2) inflammasome, which are both essential in acute lung injury (ALI). However, their interaction mechanism has remained elusive. Macrophages are known to express the AIM2 inflammasome and the main receptors [receptor for advanced glycation end products (RAGE), Toll-like receptor 2/4 (TLR-2/TLR-4)] of HMGB1 to transmit intracellular signals. The present study aimed to indicate whether HMGB1 participates in the process of lipopolysaccharides (LPS)-induced ALI through activating the AIM2 inflammasome in macrophages, as well as inducing polarization of M1 macrophages via TLR2, TLR4 and RAGE/nuclear factor-κB (NF-κB) signaling pathways. In an in vivo mouse model of LPS-induced ALI, anti-HMGB1, recombinant (r) HMGB1, LPS from Rhodobacter sphaeroides (LPS-RS, TLR2/4 antagonist) or FPS-ZM1 (RAGE antagonist) were administrated. In in vitro studies, bone marrow-derived macrophages from mice primed with LPS were stimulated with or without anti-HMGB1, rHMGB1, LPS-RS, or FPS-ZM1. The findings revealed that anti-HMGB1, LPS-RS and FPS-ZM1 significantly decreased infiltration of inflamematory cells, wet-to-dry ratio, myeloperoxidase activity in the lung, the levels of cytokines, as well as macrophages and neutrophil infiltration in the bronchoalveolar lavage fluid. However, rHMGB1 aggravated the inflammatory response in ALI. Mechanistically, anti-HMGB1, LPS-RS and FPS-ZM1 attenuated activation of TLR2, TLR4, and RAGE/NF-κB signaling pathways and expression of the AIM2 inflammasome in macrophages. However, rHMGB1 enhanced their expression levels and induced polarization of M1 macrophages. These results indicated that HMGB1 could participate in the pathogenesis of ALI by activating the AIM2 inflammasome in macrophages, as well as inducing polarization of M1 macrophages through TLR2, TLR4 and RAGE/NF-κB signaling pathways. |
format | Online Article Text |
id | pubmed-6889921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-68899212019-12-06 HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways Wang, Jing Li, Ruiting Peng, Zhiyong Hu, Bo Rao, Xin Li, Jianguo Int J Mol Med Articles High mobility group box 1 (HMGB1), a crucial proinflammatory cytokine, was reported to activate the absent in melanoma 2 (AIM2) inflammasome, which are both essential in acute lung injury (ALI). However, their interaction mechanism has remained elusive. Macrophages are known to express the AIM2 inflammasome and the main receptors [receptor for advanced glycation end products (RAGE), Toll-like receptor 2/4 (TLR-2/TLR-4)] of HMGB1 to transmit intracellular signals. The present study aimed to indicate whether HMGB1 participates in the process of lipopolysaccharides (LPS)-induced ALI through activating the AIM2 inflammasome in macrophages, as well as inducing polarization of M1 macrophages via TLR2, TLR4 and RAGE/nuclear factor-κB (NF-κB) signaling pathways. In an in vivo mouse model of LPS-induced ALI, anti-HMGB1, recombinant (r) HMGB1, LPS from Rhodobacter sphaeroides (LPS-RS, TLR2/4 antagonist) or FPS-ZM1 (RAGE antagonist) were administrated. In in vitro studies, bone marrow-derived macrophages from mice primed with LPS were stimulated with or without anti-HMGB1, rHMGB1, LPS-RS, or FPS-ZM1. The findings revealed that anti-HMGB1, LPS-RS and FPS-ZM1 significantly decreased infiltration of inflamematory cells, wet-to-dry ratio, myeloperoxidase activity in the lung, the levels of cytokines, as well as macrophages and neutrophil infiltration in the bronchoalveolar lavage fluid. However, rHMGB1 aggravated the inflammatory response in ALI. Mechanistically, anti-HMGB1, LPS-RS and FPS-ZM1 attenuated activation of TLR2, TLR4, and RAGE/NF-κB signaling pathways and expression of the AIM2 inflammasome in macrophages. However, rHMGB1 enhanced their expression levels and induced polarization of M1 macrophages. These results indicated that HMGB1 could participate in the pathogenesis of ALI by activating the AIM2 inflammasome in macrophages, as well as inducing polarization of M1 macrophages through TLR2, TLR4 and RAGE/NF-κB signaling pathways. D.A. Spandidos 2020-01 2019-11-12 /pmc/articles/PMC6889921/ /pubmed/31746367 http://dx.doi.org/10.3892/ijmm.2019.4402 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Wang, Jing Li, Ruiting Peng, Zhiyong Hu, Bo Rao, Xin Li, Jianguo HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways |
title | HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways |
title_full | HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways |
title_fullStr | HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways |
title_full_unstemmed | HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways |
title_short | HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signaling pathways |
title_sort | hmgb1 participates in lps-induced acute lung injury by activating the aim2 inflammasome in macrophages and inducing polarization of m1 macrophages via tlr2, tlr4, and rage/nf-κb signaling pathways |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889921/ https://www.ncbi.nlm.nih.gov/pubmed/31746367 http://dx.doi.org/10.3892/ijmm.2019.4402 |
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