Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783303515566768128 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5833701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT suli kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT lina kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT tanghua kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT louziyang kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT chongxiaodan kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT zhangchenxi kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT sujiacan kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells AT dongxin kupffercellderivedtnfapromoteshepatocytestoproducecxcl1andmobilizeneutrophilsinresponsetonecroticcells |