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Role of PECAM-1 in radiation-induced liver inflammation
Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-depe...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594685/ https://www.ncbi.nlm.nih.gov/pubmed/26177067 http://dx.doi.org/10.1111/jcmm.12630 |
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author | Malik, Ihtzaz Ahmed Stange, Ina Martius, Gesa Cameron, Silke Rave-Fränk, Margret Hess, Clemens Friedrich Ellenrieder, Volker Wolff, Hendrik Andreas |
author_facet | Malik, Ihtzaz Ahmed Stange, Ina Martius, Gesa Cameron, Silke Rave-Fränk, Margret Hess, Clemens Friedrich Ellenrieder, Volker Wolff, Hendrik Andreas |
author_sort | Malik, Ihtzaz Ahmed |
collection | PubMed |
description | Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation. Immunohistologically, an increased number of neutrophil granulocytes (NG) (but not of mononuclear phagocytes) was observed in the liver of WT and PECAM-1-KO mice at 6 hrs after irradiation. The number of recruited NG was higher and prolonged until 24 hrs in KO compared to WT-mice. Correspondingly, a significant induction of hepatic tumour necrosis factor (TNF)-α and CXC-chemokines (KC/CXCL1 interleukin-8/CXCL8) was detected together with an elevation of serum liver transaminases (6–24 hrs) in WT and KO-mice. Likewise, phosphorylation of signal transducer and activator of transcription-3 (STAT-3) was observed in both animal groups after irradiation. The level of all investigated proteins as well as of the liver transaminases was significantly higher in KO than WT-mice. In the cell-line U937, irradiation led to a reduction in PECAM-1 in parallel to an increased ICAM-1 expression. TNF-α-blockage by anti-TNF-α prevented this change in both proteins in cell culture. Radiation-induced stress conditions induce a transient accumulation of granulocytes within the liver by down-regulation/absence of PECAM-1. It suggests that reduction/lack in PECAM-1 may lead to greater and prolonged inflammation which can be prevented by anti-TNFα. |
format | Online Article Text |
id | pubmed-4594685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45946852015-10-09 Role of PECAM-1 in radiation-induced liver inflammation Malik, Ihtzaz Ahmed Stange, Ina Martius, Gesa Cameron, Silke Rave-Fränk, Margret Hess, Clemens Friedrich Ellenrieder, Volker Wolff, Hendrik Andreas J Cell Mol Med Original Articles Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is known to play an important role in hepatic inflammation. Therefore, we investigated the role of PECAM-1 in wild-type (WT) and knock-out (KO)-mice after single-dose liver irradiation (25 Gy). Both, at mRNA and protein level, a time-dependent decrease in hepatic PECAM-1, corresponding to an increase in intercellular cell adhesion molecule-1 (ICAM-1) (6 hrs) was detected in WT-mice after irradiation. Immunohistologically, an increased number of neutrophil granulocytes (NG) (but not of mononuclear phagocytes) was observed in the liver of WT and PECAM-1-KO mice at 6 hrs after irradiation. The number of recruited NG was higher and prolonged until 24 hrs in KO compared to WT-mice. Correspondingly, a significant induction of hepatic tumour necrosis factor (TNF)-α and CXC-chemokines (KC/CXCL1 interleukin-8/CXCL8) was detected together with an elevation of serum liver transaminases (6–24 hrs) in WT and KO-mice. Likewise, phosphorylation of signal transducer and activator of transcription-3 (STAT-3) was observed in both animal groups after irradiation. The level of all investigated proteins as well as of the liver transaminases was significantly higher in KO than WT-mice. In the cell-line U937, irradiation led to a reduction in PECAM-1 in parallel to an increased ICAM-1 expression. TNF-α-blockage by anti-TNF-α prevented this change in both proteins in cell culture. Radiation-induced stress conditions induce a transient accumulation of granulocytes within the liver by down-regulation/absence of PECAM-1. It suggests that reduction/lack in PECAM-1 may lead to greater and prolonged inflammation which can be prevented by anti-TNFα. John Wiley & Sons, Ltd 2015-10 2015-07-14 /pmc/articles/PMC4594685/ /pubmed/26177067 http://dx.doi.org/10.1111/jcmm.12630 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Malik, Ihtzaz Ahmed Stange, Ina Martius, Gesa Cameron, Silke Rave-Fränk, Margret Hess, Clemens Friedrich Ellenrieder, Volker Wolff, Hendrik Andreas Role of PECAM-1 in radiation-induced liver inflammation |
title | Role of PECAM-1 in radiation-induced liver inflammation |
title_full | Role of PECAM-1 in radiation-induced liver inflammation |
title_fullStr | Role of PECAM-1 in radiation-induced liver inflammation |
title_full_unstemmed | Role of PECAM-1 in radiation-induced liver inflammation |
title_short | Role of PECAM-1 in radiation-induced liver inflammation |
title_sort | role of pecam-1 in radiation-induced liver inflammation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594685/ https://www.ncbi.nlm.nih.gov/pubmed/26177067 http://dx.doi.org/10.1111/jcmm.12630 |
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