Role of PECAM‐1 in radiation‐induced liver inflammation

• Published in: Journal of cellular and molecular medicine 2015-10, Vol.19 (10), p.2441-2452
• Main Authors: Malik, Ihtzaz Ahmed, Stange, Ina, Martius, Gesa, Cameron, Silke, Rave‐Fränk, Margret, Hess, Clemens Friedrich, Ellenrieder, Volker, Wolff, Hendrik Andreas
• Format: Article
• Language: English
• Subjects: Adhesion; adhesion molecules; Animals; Blotting, Western; Cell adhesion; Cell adhesion & migration; Cell adhesion molecules; Cell culture; Chemokine CXCL1 - blood; Chemokines; Cytokines; Endothelial cells; Fluorescent Antibody Technique; Gene expression; Gene Expression Regulation - radiation effects; Granulocytes; Hepatocytes; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Irradiation; Kinetics; Leukocytes; Leukocytes (granulocytic); Leukocytes (mononuclear); Liver; Liver - enzymology; Liver - metabolism; Liver - pathology; Liver - radiation effects; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - metabolism; Monocytes - radiation effects; Neutrophils; Original; Phagocytes; Phosphorylation; Phosphorylation - radiation effects; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Proteins; Radiation; Radiation, Ionizing; Recruitment; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; STAT3 Transcription Factor - metabolism; Transcription; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; U937 Cells
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12630

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.