title: Role of PECAM-1 in radiation-induced liver inflammation.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Ihtzaz Ahmed
authors.initials: IA
authors.lastname: Malik
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Stange
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Gesa
authors.initials: G
authors.lastname: Martius
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Rave-Fränk
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Clemens Friedrich
authors.initials: CF
authors.lastname: Hess
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Ellenrieder
authors.affiliation: Department of Radiotherapy and Radiooncology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Hendrik Andreas
authors.initials: HA
authors.lastname: Wolff
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054360:Chemokine CXCL1 / Q000097:blood; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism / Q000528:radiation effects; D010766:Phosphorylation / Q000528:radiation effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1
keywords: adhesion molecules; cytokines; liver; radiation