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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...

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Autores principales: Malik, Ihtzaz Ahmed, Stange, Ina, Martius, Gesa, Cameron, Silke, Rave-Fränk, Margret, Hess, Clemens Friedrich, Ellenrieder, Volker, Wolff, Hendrik Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
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.
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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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