Ghayyor Ahmad

Cellular and molecular mechanisms regulating the hepatic erythropoietin expression during acute-phase response: a role for IL-6.

The source of circulating erythropoietin (EPO), the mediators and the mechanisms involved in the upregulation of EPO gene expression during acute-phase reaction are still poorly understood. Acute-phase reaction was induced by either intramuscular turpentine oil (TO) or intraperitoneal lipopolysaccharide (LPS) administration into wild-type and interleukin (IL)-6 knockout (KO) mice. Animals were killed at different time points and blood, liver and muscle tissue were collected. Serum levels of EPO were measured by enzyme-linked immunoadsorbent assay; liver and injured muscle samples were processed for RNA isolation and for protein analysis. EPO, hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) mRNA were analyzed by RT–PCR and the protein levels were analyzed by western blot and electrophoretic mobility shift assay. HIF-1α and HIF-2α localization was performed through immunofluorescence staining. EPO, HIF-1 and HIF-2 gene and protein expression levels were also analyzed in isolated mouse hepatocytes after stimulation with IL-6. In the wild-type animals, EPO serum levels increased dramatically at 12 h after the insults together with the hepatic gene expression. In TO-treated animals, the EPO gene expression reached an 8.2-fold increase at 12 h, and in LPS-treated mice a similar induction was recorded at 6 h (about 4.5-fold increase). In the IL-6KO strain, the upregulation after the inflammatory stimuli was much lower (only 2.0-fold increase). A progressive upregulation of HIF-1α and HIF-2α was detectable until 6 h after the insults, but only HIF-1α upregulation was reduced in IL-6KO mice. In isolated hepatocytes, stimulation with a single dose of IL-6 induced a nuclear accumulation of HIF-1α, in parallel with an increase of EPO mRNA. No effect on HIF-2α expression was found. IL-6 appears to be the main regulator of EPO gene expression and a major contributor for HIF-1α induction in hepatocytes and Kupffer cells during acute-phase response. The increase of HIF-2α, predominantly expressed in endothelial cells and fibroblast-like cells, seems not to be affected by the lack of IL-6.

LIPOCALIN-2 IS A MAJOR ACUTE-PHASE PROTEIN IN A RAT AND MOUSE MODEL OF STERILE ABSCESS

Lipocalin-2 (LCN-2) is a 25-kDa secretory protein currently used as a biomarker for renal injury and inflammation. Its source and cause of the increased serum levels are unclear. The current study compares LCN-2 gene expression with known major acute-phase proteins in the liver in a rat and mouse model of turpentine oil–induced sterile abscess. Serum LCN-2 concentrations increased dramatically up to 200-fold (20 &mgr;g/mL) at 48 h after turpentine oil injection. A strong elevation of LCN-2 mRNA in rat liver was observed starting from 4 h up to 48 h after injection, with a maximum (8,738 ± 2,104-fold) at 24 h, which was further confirmed by Western blot analysis. In contrast, the increases in gene expression of &agr;2-macroglobulin, the major acute-phase protein, and hemoxygenase 1, a positive acute-phase protein, were only 1,025 ± 505-fold and 47 ± 12-fold, respectively, during acute-phase reaction (APR). No considerable change was observed in LCN-2 mRNA in rat kidney and other organs as compared with liver. Using wild-type mice, a massive increase in gene expression of LCN-2, with a maximum of 2,498 ± 84-fold in liver, which is similar to that for serum amyloid A (2,825 ± 233-fold), a major mouse acute-phase protein. However, such an increase was significantly inhibited in interleukin 6 knockout mice during APR. Interleukin 6–treated rat hepatocytes induced a significant time-dependent upregulation of LCN-2. Lipocalin-2 is the major acute-phase protein in rat as compared with &agr;2-macroglobulin and hemoxygenase 1 and comparable with serum amyloid A in mouse whose gene expression is mainly controlled by interleukin 6. The liver is the main source of serum LCN-2 in the case of APR. &NA; ABBREVIATIONS—LCN-2—lipocalin-2—&agr;2M—&agr;2-macroglobulin—HO-1—hemoxygenase 1—IL-6—interleukin 6—SAA—serum amyloid A—TO—turpentine oil—APR—acute-phase reaction

Hepatic changes of erythropoietin gene expression in a rat model of acute‐phase response

An acute‐phase response is the systemic reaction of an organism to insult (e.g. infection, trauma and burning). It represents the ‘first line’ of defence of the body to tissue‐damaging attacks. In the present work, we used a rat model of an intra‐muscular turpentine oil (TO) injection to analyse erythropoietin (EPO) gene expression changes in the liver, one of the main target organs of acute‐phase cytokines. EPO began to increase in the serum of TO‐treated animals 6 h after injection and reached a maximum at 24 h (125±20 pg/ml). The detection of total RNA by polymerase chain reaction analysis showed that the levels of EPO gene expression in the liver were considerably increased between 2 and 12 h by up to 20‐fold at the peak after TO administration, followed by a gradual decrease over the next 48 h, although the values remained significantly higher compared with the control group. In the kidney, after a sudden slight increase, the values declined progressively to 3.5‐fold decrease at 12 h after the injection. In the liver, a parallel upregulation of the hypoxia‐inducible factor‐1 (HIF‐1) α gene was observed (up to 4.7‐fold increase), while HIF‐2 α gene expression remained unaltered. On the other hand, the protein of both genes became detectable after the injection and increased progressively over 24 h, with a subsequent decline. These results suggest that EPO may be added to the increasing group of positive acute‐phase proteins and the liver might represent the major source of the hormone under these conditions in the rat.

Effect of irradiation on gene expression of rat liver adhesion molecules: in vivo and in vitro studies.

Background and Purpose:Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro.Material and Methods:Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology.Results:Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), β1-integrin, β2-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, β1-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), β2-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-)α, interleukin-(IL-)1β, or IL-6 plus TNF-α led to an upregulation of P-selectin, ICAM-1 and VCAM-1.Conclusion:The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of inflammation in the irradiated rat liver.Hintergrund und Ziel:Tierexperimentelle Studien haben gezeigt, dass es in der Akutphase nach Einzeitbestrahlung der Leber mit 25 Gy im Gegensatz zu anderen toxischen Leberschädigungen trotz strahleninduzierter Expression von Chemokinen nicht zu einer inflammatorischen Reaktion mit Einwanderung von Entzündungszellen kommt. Ziel der vorliegenden experimentellen Studie war die Messung der Auswirkungen ionisierender Strahlung auf die Expression der wichtigsten Adhäsionsmoleküle nach Leberbestrahlung in vivo und Bestrahlung von Hepatozyten in vitro im etablierten Modell.Material und Methodik:Innerhalb von 48 h nach selektiver Leberbestrahlung in vivo (25 Gy) sowie Bestrahlung von Hepatozyten in vitro (8 Gy) wurde RNA extrahiert und mittels Real-Time-PCR (Polymerase-Kettenreaktion) und Northern-Blot analysiert. Neben alleinig bestrahlten Hepatozyten wurden dabei in vitro auch Zellen untersucht, die zusätzlich zur Bestrahlung mit Tumor-Nekrose-Faktor-(TNF-)α, Interleukin-(IL-)1β oder einer Kombination aus IL-6/TNF-α inkubiert wurden. Adhäsionsmolekülkonzentrationen im Serum wurden mittels ELISA („enzyme-linked immunosorbent assay“) gemessen, Lebergewebe auch mittels Immunhistochemie untersucht.Ergebnisse:ICAM-1 („intercellular adhesion molecule-1“), VCAM-1 („vascular cell adhesion molecule-1“), JAM-1, („junctional adhesion molecule-1“), β1-Integrin, β2-Integrin, E-Cadherin und P-Selectin waren in vivo nach Bestrahlung vermehrt exprimiert, die PECAM-1-Expression („platelet-endothelial cell adhesion molecule-1“) blieb jedoch unverändert. In vitro kam es zu einer vermehrten Expression von β1-Integrin, JAM-1 und ICAM-2 und einer verminderten Expression von P-Selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 („mucosal addressin cell adhesion molecule 1“), β2-Integrin und E-Cadherin. Nach zusätzlicher Inkubation der Hepatozyten mit TNF-α, IL-1β oder IL-6 und TNF-α kam es auch in vitro zu einer vermehrten Expression von P-Selectin, ICAM-1 und VCAM-1.Schlussfolgerung:Leberbestrahlung führt zu einer vermehrten Expression der wichtigsten Adhäsionsmoleküle in vivo und in durch Zytokine aktivierten Hepatozyten. Die PECAM-1-Expression wird allerdings nicht beeinflusst. Dies könnte einer der Gründe für die fehlende Inflammation in diesem Modell sein.

Effect of Irradiation on Gene Expression of Rat Liver Adhesion Molecules

Background and Purpose:Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro.Material and Methods:Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology.Results:Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), β1-integrin, β2-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, β1-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), β2-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-)α, interleukin-(IL-)1β, or IL-6 plus TNF-α led to an upregulation of P-selectin, ICAM-1 and VCAM-1.Conclusion:The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of inflammation in the irradiated rat liver.Hintergrund und Ziel:Tierexperimentelle Studien haben gezeigt, dass es in der Akutphase nach Einzeitbestrahlung der Leber mit 25 Gy im Gegensatz zu anderen toxischen Leberschädigungen trotz strahleninduzierter Expression von Chemokinen nicht zu einer inflammatorischen Reaktion mit Einwanderung von Entzündungszellen kommt. Ziel der vorliegenden experimentellen Studie war die Messung der Auswirkungen ionisierender Strahlung auf die Expression der wichtigsten Adhäsionsmoleküle nach Leberbestrahlung in vivo und Bestrahlung von Hepatozyten in vitro im etablierten Modell.Material und Methodik:Innerhalb von 48 h nach selektiver Leberbestrahlung in vivo (25 Gy) sowie Bestrahlung von Hepatozyten in vitro (8 Gy) wurde RNA extrahiert und mittels Real-Time-PCR (Polymerase-Kettenreaktion) und Northern-Blot analysiert. Neben alleinig bestrahlten Hepatozyten wurden dabei in vitro auch Zellen untersucht, die zusätzlich zur Bestrahlung mit Tumor-Nekrose-Faktor-(TNF-)α, Interleukin-(IL-)1β oder einer Kombination aus IL-6/TNF-α inkubiert wurden. Adhäsionsmolekülkonzentrationen im Serum wurden mittels ELISA („enzyme-linked immunosorbent assay“) gemessen, Lebergewebe auch mittels Immunhistochemie untersucht.Ergebnisse:ICAM-1 („intercellular adhesion molecule-1“), VCAM-1 („vascular cell adhesion molecule-1“), JAM-1, („junctional adhesion molecule-1“), β1-Integrin, β2-Integrin, E-Cadherin und P-Selectin waren in vivo nach Bestrahlung vermehrt exprimiert, die PECAM-1-Expression („platelet-endothelial cell adhesion molecule-1“) blieb jedoch unverändert. In vitro kam es zu einer vermehrten Expression von β1-Integrin, JAM-1 und ICAM-2 und einer verminderten Expression von P-Selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 („mucosal addressin cell adhesion molecule 1“), β2-Integrin und E-Cadherin. Nach zusätzlicher Inkubation der Hepatozyten mit TNF-α, IL-1β oder IL-6 und TNF-α kam es auch in vitro zu einer vermehrten Expression von P-Selectin, ICAM-1 und VCAM-1.Schlussfolgerung:Leberbestrahlung führt zu einer vermehrten Expression der wichtigsten Adhäsionsmoleküle in vivo und in durch Zytokine aktivierten Hepatozyten. Die PECAM-1-Expression wird allerdings nicht beeinflusst. Dies könnte einer der Gründe für die fehlende Inflammation in diesem Modell sein.

Regulation of iron uptake in primary culture rat hepatocytes: the role of acute-phase cytokines.

ABSTRACT Decreased serum and increased hepatic iron uptake is the hallmark of acute-phase (AP) response. Iron uptake is controlled by iron transport proteins such as transferrin receptors (TfRs) and lipocalin 2 (LCN-2). The current study aimed to understand the regulation of iron uptake in primary culture hepatocytes in the presence/absence of AP mediators. Rat hepatocytes were stimulated with different concentrations of iron alone (0.01, 0.1, 0.5 mM) and AP cytokines (interleukin 6 [IL-6], IL-1&bgr;, tumor necrosis factor &agr;) in the presence/absence of iron (FeCl3: 0.1 mM). Hepatocytes were harvested at different time points (0, 6, 12, 24 h). Total mRNA and proteins were extracted for reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot. A significant iron uptake was detected with 0.1 mM iron administration with a maximum (133.37 ± 4.82 µg/g of protein) at 24 h compared with control and other iron concentrations. This uptake was further enhanced in the presence of AP cytokines with a maximum iron uptake (481 ± 25.81 µg/g of protein) after concomitant administration of IL-6 + iron to cultured hepatocytes. Concomitantly, gene expression of LCN-2 and ferritin subunits (light- and heavy-chain ferritin subunits) was upregulated by iron or/and AP cytokines with a maximum at 24 h both at mRNA and protein levels. In contrast, a decreased TfR1 level was detected by IL-6 and iron alone, whereas combination of iron and AP cytokines (mainly IL-6) abrogated the downregulation of TfR1. An increase in LCN-2 release into the supernatant of cultured hepatocytes was observed after addition of iron/AP cytokines into the medium. This increase in secretion was further enhanced by combination of IL-6 + iron. In conclusion, iron uptake is tightly controlled by already present iron concentration in the culture. This uptake can be further enhanced by AP cytokines, mainly by IL-6.

Phagocytosis of gadolinium chloride or zymosan induces simultaneous upregulation of hepcidin- and downregulation of hemojuvelin- and Fpn-1-gene expression in murine liver.

The liver and the spleen are the organs in which cellular material and aged erythrocytes are eliminated from the blood. Within the liver, Kupffer cells (KCs) are mainly responsible for this task, as such KCs have a pivotal role in iron metabolism. The aim of this study is to investigate the changes of hepatic gene expression in two models of KC phagocytosis. Gadolinium chloride (GD) or zymosan was injected intraperitoneally into rats and to endotoxin-resistant mice (C3H/HeJ). The animals were killed at different time points and their livers were immediately frozen in liquid nitrogen for RNA isolation and immunohistological studies. RNA was analyzed by real-time PCR and northern blot. Sera were used to measure transaminases, hepcidin and iron levels. The expression of iron metabolism genes, hepcidin, hemojuvelin (Hjv), ferroportin-1 (Fpn-1) and of the inflammatory cytokines IL-6, IL-1β, TNF-α and IFN-γ was determined. Although phagocytosed material was detected in ED-1- and C1q-positive cells, no inflammatory cells were identified within the liver parenchyma. Serum levels of hepcidin, iron and transaminases did not differ from those of control animals. Both GD and zymosan induced an upregulation of hepcidin-gene expression in rat liver as early as 3 h, reaching a maximum 6 h after treatment. Hjv- and Fpn-1-gene expression was downregulated at the same time. IL-6 was by far the most induced acute-phase-cytokine in GD- and zymosan-treated livers, although IL-1β and TNF-α were also strongly upregulated by zymosan and to a lesser extent by GD. Similar results were obtained in the C3H/HeJ mouse strain excluding the possible role of contaminating endotoxin. This study shows that phagocytosis upregulates hepcidin-gene expression and downregulates Hjv- and Fpn-1-gene expression within the liver. These changes in iron-regulating-gene expression may be mediated by the locally produced acute-phase-cytokines.

Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction

Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression.

Effect of Irradiation on Gene Expression of Rat Liver Adhesion Molecules@@@Einfluss ionisierender Strahlung auf die Expression von Adhäsionsmolekülen in der Leber. In-vivo- und In-vitro-Studien: In Vivo and In Vitro Studies

Background and Purpose:Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro.Material and Methods:Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology.Results:Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), β1-integrin, β2-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, β1-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), β2-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-)α, interleukin-(IL-)1β, or IL-6 plus TNF-α led to an upregulation of P-selectin, ICAM-1 and VCAM-1.Conclusion:The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of inflammation in the irradiated rat liver.Hintergrund und Ziel:Tierexperimentelle Studien haben gezeigt, dass es in der Akutphase nach Einzeitbestrahlung der Leber mit 25 Gy im Gegensatz zu anderen toxischen Leberschädigungen trotz strahleninduzierter Expression von Chemokinen nicht zu einer inflammatorischen Reaktion mit Einwanderung von Entzündungszellen kommt. Ziel der vorliegenden experimentellen Studie war die Messung der Auswirkungen ionisierender Strahlung auf die Expression der wichtigsten Adhäsionsmoleküle nach Leberbestrahlung in vivo und Bestrahlung von Hepatozyten in vitro im etablierten Modell.Material und Methodik:Innerhalb von 48 h nach selektiver Leberbestrahlung in vivo (25 Gy) sowie Bestrahlung von Hepatozyten in vitro (8 Gy) wurde RNA extrahiert und mittels Real-Time-PCR (Polymerase-Kettenreaktion) und Northern-Blot analysiert. Neben alleinig bestrahlten Hepatozyten wurden dabei in vitro auch Zellen untersucht, die zusätzlich zur Bestrahlung mit Tumor-Nekrose-Faktor-(TNF-)α, Interleukin-(IL-)1β oder einer Kombination aus IL-6/TNF-α inkubiert wurden. Adhäsionsmolekülkonzentrationen im Serum wurden mittels ELISA („enzyme-linked immunosorbent assay“) gemessen, Lebergewebe auch mittels Immunhistochemie untersucht.Ergebnisse:ICAM-1 („intercellular adhesion molecule-1“), VCAM-1 („vascular cell adhesion molecule-1“), JAM-1, („junctional adhesion molecule-1“), β1-Integrin, β2-Integrin, E-Cadherin und P-Selectin waren in vivo nach Bestrahlung vermehrt exprimiert, die PECAM-1-Expression („platelet-endothelial cell adhesion molecule-1“) blieb jedoch unverändert. In vitro kam es zu einer vermehrten Expression von β1-Integrin, JAM-1 und ICAM-2 und einer verminderten Expression von P-Selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 („mucosal addressin cell adhesion molecule 1“), β2-Integrin und E-Cadherin. Nach zusätzlicher Inkubation der Hepatozyten mit TNF-α, IL-1β oder IL-6 und TNF-α kam es auch in vitro zu einer vermehrten Expression von P-Selectin, ICAM-1 und VCAM-1.Schlussfolgerung:Leberbestrahlung führt zu einer vermehrten Expression der wichtigsten Adhäsionsmoleküle in vivo und in durch Zytokine aktivierten Hepatozyten. Die PECAM-1-Expression wird allerdings nicht beeinflusst. Dies könnte einer der Gründe für die fehlende Inflammation in diesem Modell sein.