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Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells

The damage-associated molecular pattern molecules (DAMPs) released by necrotic cells can trigger inflammatory response, which will facilitate the clearance of these dead cells. Neutrophil mobilization is a very important step for the dead cell clearance, however the detailed mechanisms for DAMPs ind...

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Autores principales: Su, Li, Li, Na, Tang, Hua, Lou, Ziyang, Chong, Xiaodan, Zhang, Chenxi, Su, Jiacan, Dong, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833701/
https://www.ncbi.nlm.nih.gov/pubmed/29476069
http://dx.doi.org/10.1038/s41419-018-0377-4
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author Su, Li
Li, Na
Tang, Hua
Lou, Ziyang
Chong, Xiaodan
Zhang, Chenxi
Su, Jiacan
Dong, Xin
author_facet Su, Li
Li, Na
Tang, Hua
Lou, Ziyang
Chong, Xiaodan
Zhang, Chenxi
Su, Jiacan
Dong, Xin
author_sort Su, Li
collection PubMed
description The damage-associated molecular pattern molecules (DAMPs) released by necrotic cells can trigger inflammatory response, which will facilitate the clearance of these dead cells. Neutrophil mobilization is a very important step for the dead cell clearance, however the detailed mechanisms for DAMPs induce neutrophil mobilization remains largely elusive. In this study, by using a necrotic cell-induced neutrophil mobilization mice model, we found that both neutrophil number and percentage rapidly (as early as 30 min) increased with necrotic cells but not live cell treatment. CXCL1 was rapidly increased in the serum and was responsible for the neutrophil mobilization when treated with necrotic cells. We further demonstrated that the hepatocytes in the liver were the main source of CXCL1 production in response to necrotic cells challenge. However, the hepatocytes did not express CXCL1 when incubating with necrotic cells alone. When Kupffer cells were ablated, the increased CXCL1 levels as well as neutrophil mobilization were abolished with necrotic cells challenge. Moreover, we clarified Kupffer cells-derived TNF-α activates the NF-κB pathway in hepatocytes and promote hepatocytes to express CXCL1. In summary, we showed that the liver is the main source for necrotic cell-induced CXCL1 production and neutrophil mobilization. Kupffer cells in the liver sense DAMPs and release TNF-α to activate the NF-κB pathway in hepatocytes. The interaction between Kupffer cells and hepatocytes is critical for CXCL1 production.
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spelling pubmed-58337012018-03-06 Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells Su, Li Li, Na Tang, Hua Lou, Ziyang Chong, Xiaodan Zhang, Chenxi Su, Jiacan Dong, Xin Cell Death Dis Article The damage-associated molecular pattern molecules (DAMPs) released by necrotic cells can trigger inflammatory response, which will facilitate the clearance of these dead cells. Neutrophil mobilization is a very important step for the dead cell clearance, however the detailed mechanisms for DAMPs induce neutrophil mobilization remains largely elusive. In this study, by using a necrotic cell-induced neutrophil mobilization mice model, we found that both neutrophil number and percentage rapidly (as early as 30 min) increased with necrotic cells but not live cell treatment. CXCL1 was rapidly increased in the serum and was responsible for the neutrophil mobilization when treated with necrotic cells. We further demonstrated that the hepatocytes in the liver were the main source of CXCL1 production in response to necrotic cells challenge. However, the hepatocytes did not express CXCL1 when incubating with necrotic cells alone. When Kupffer cells were ablated, the increased CXCL1 levels as well as neutrophil mobilization were abolished with necrotic cells challenge. Moreover, we clarified Kupffer cells-derived TNF-α activates the NF-κB pathway in hepatocytes and promote hepatocytes to express CXCL1. In summary, we showed that the liver is the main source for necrotic cell-induced CXCL1 production and neutrophil mobilization. Kupffer cells in the liver sense DAMPs and release TNF-α to activate the NF-κB pathway in hepatocytes. The interaction between Kupffer cells and hepatocytes is critical for CXCL1 production. Nature Publishing Group UK 2018-02-23 /pmc/articles/PMC5833701/ /pubmed/29476069 http://dx.doi.org/10.1038/s41419-018-0377-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Su, Li
Li, Na
Tang, Hua
Lou, Ziyang
Chong, Xiaodan
Zhang, Chenxi
Su, Jiacan
Dong, Xin
Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells
title Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells
title_full Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells
title_fullStr Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells
title_full_unstemmed Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells
title_short Kupffer cell-derived TNF-α promotes hepatocytes to produce CXCL1 and mobilize neutrophils in response to necrotic cells
title_sort kupffer cell-derived tnf-α promotes hepatocytes to produce cxcl1 and mobilize neutrophils in response to necrotic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833701/
https://www.ncbi.nlm.nih.gov/pubmed/29476069
http://dx.doi.org/10.1038/s41419-018-0377-4
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