Malik, Ihtzaz Ahmed

[["dc.bibliographiccitation.firstpage","321"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Radiation and Environmental Biophysics"],["dc.bibliographiccitation.lastpage","338"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Moriconi, Federico"],["dc.date.accessioned","2018-11-07T09:22:03Z"],["dc.date.available","2018-11-07T09:22:03Z"],["dc.date.issued","2013"],["dc.description.abstract","The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far. Rats were exposed to selective liver FI (total dose 60 Gy, 2 Gy/day) or HDI (25 Gy) and were killed three months after the end of irradiation. To study acute effects, HDI-treated rats were additionally killed at several time points between 1 and 48 h. Three months after irradiation, no differences between FI and HDI treatment were found for macroscopically detectable small \"scars\" on the liver surface and for an increased number of neutrophil granulocytes distributed in the portal fields and through the liver parenchyma. As well, no changes in HE-stained tissues or clear signs of fibrosis were found around the portal vessels. Differences were seen for the number of bile ducts being increased in FI- but not in HDI-treated livers. Serum levels indicative of liver damage were determined for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gamma GT) and lactate dehydrogenase (LDH). A significant increase of AP was detected only after FI while HDI led to the significant increases of AST and LDH serum levels. By performing RT-PCR, we detected up-regulation of matrix metalloproteinases, MMP-2, MMP-9, MMP-14, and of their inhibitors, TIMP-1, TIMP-2 and TIMP-3, shortly after HDI, but not at 3 month after FI or HDI. Overall, we saw punctual differences after FI and HDI, and a diffuse formation of small scars at the liver surface. Lack of \"provisional clot\"-formation and absence of recruitment of mononuclear phagocytes could be one explanation for scar formation as incomplete repair response to irradiation."],["dc.identifier.doi","10.1007/s00411-013-0468-7"],["dc.identifier.isi","000322033000004"],["dc.identifier.pmid","23595725"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29250"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0301-634X"],["dc.title","Rat model of fractionated (2 Gy/day) 60 Gy irradiation of the liver: long-term effects"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7347"],["dc.bibliographiccitation.issue","41"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","7358"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Naz, Naila"],["dc.date.accessioned","2019-07-09T11:44:36Z"],["dc.date.available","2019-07-09T11:44:36Z"],["dc.date.issued","2017"],["dc.description.abstract","AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair. METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide (TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain (FTL), and ferritin heavy chain (FTH) was investigated in the liver by qRT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations. RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase (aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ (1h) and IL-1β (3h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter (96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes. CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins."],["dc.identifier.doi","10.3748/wjg.v23.i41.7347"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14835"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59046"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2219-2840"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","Reabsorption of iron into acutely damaged rat liver: A role for ferritins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","217"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","233"],["dc.bibliographiccitation.volume","137"],["dc.contributor.author","Wojcik, Marta"],["dc.contributor.author","Ramadori, Pierluigi"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Martius, Gesa"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Schultze, Frank Christian"],["dc.date.accessioned","2018-11-07T09:14:07Z"],["dc.date.available","2018-11-07T09:14:07Z"],["dc.date.issued","2012"],["dc.description.abstract","It has been suggested that cyclooxygenase-2 (COX-2)-mediated prostaglandin synthesis is associated with liver inflammation and carcinogenesis. The aim of this study is to identify the cellular source of COX-2 expression in different stages, from acute liver injury through liver fibrosis to cholangiocarcinoma (CC). We induced in rats acute and \"chronic\" liver injury (thioacetamide (TAA) or carbon tetrachloride (CCl(4))) and CC development (TAA) and assessed COX-2 gene expression in normal and damaged liver tissue by RT-PCR of total RNA. The cellular localization of COX-2 protein in liver tissue was analyzed by immunohistochemistry as well as in isolated rat liver cells by Western blotting. The findings were compared with those obtained in human cirrhotic liver tissue. The specificity of the antibodies was tested by 2-DE Western blot and mass spectrometric identification of the positive protein spots. RT-PCR analysis of total RNA revealed an increase of hepatic COX-2 gene expression in acutely as well as \"chronically\" damaged liver. COX-2-protein was detected in those ED1(+)/ED2(+) cells located in the non-damaged tissue (resident tissue macrophages). In addition COX-2 positivity in inflammatory mononuclear phagocytes (ED1(+)/ED2(-)), which were also present within the tumoral tissue was detected. COX-2 protein was clearly detectable in isolated Kupffer cells as well as (at lower level) in isolated \"inflammatory\" macrophages. Similar results were obtained in human cirrhotic liver. COX-2 protein is constitutively detectable in liver tissue macrophages. Inflammatory mononuclear phagocytes contribute to the increase of COX-2 gene expression in acute and chronic liver damage induced by different toxins and in the CC microenvironment."],["dc.description.sponsorship","Ministry of Science and Higher Education, Poland [N N308 3169 33]"],["dc.identifier.doi","10.1007/s00418-011-0889-9"],["dc.identifier.isi","000299371500008"],["dc.identifier.pmid","22131058"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8811"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27328"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Immunodetection of cyclooxygenase-2 (COX-2) is restricted to tissue macrophages in normal rat liver and to recruited mononuclear phagocytes in liver injury and cholangiocarcinoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","337"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Shock"],["dc.bibliographiccitation.lastpage","345"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Ahmad, Ghayyor"],["dc.contributor.author","Alwahsh, Salamah Mohammad"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:41:37Z"],["dc.date.available","2018-11-07T09:41:37Z"],["dc.date.issued","2014"],["dc.description.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, tumor necrosis factor ) 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 mu g/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 mu g/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."],["dc.identifier.doi","10.1097/SHK.0000000000000107"],["dc.identifier.isi","000335648600011"],["dc.identifier.pmid","24365882"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33775"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1540-0514"],["dc.relation.issn","1073-2322"],["dc.title","REGULATION OF IRON UPTAKE IN PRIMARY CULTURE RAT HEPATOCYTES: THE ROLE OF ACUTE-PHASE CYTOKINES"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","842"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Laboratory Investigation"],["dc.bibliographiccitation.lastpage","856"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Sheikh, Nadeem"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Schultze, Frank"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T09:09:49Z"],["dc.date.available","2018-11-07T09:09:49Z"],["dc.date.issued","2012"],["dc.description.abstract","Liver is the central organ of iron metabolism. During acute-phase-response (APR), serum iron concentration rapidly decreases. The current study aimed to compare expression and localization of iron transport protein ferroportin-1 (Fpn-1) and of other iron import proteins after experimental tissue damage induced by injecting turpentine oil in the hind limbs of rats and mice. Serum and spleen iron concentration decreased with an increase in total liver, cytoplasmic and nuclear iron concentration. In liver, mRNA amount of Fpn-1, Fpn-1a, Fpn-1b, HFE, hemojuvelin (HJV) and hephaestin (heph) genes showed a rapid decrease. Hepcidin, divalent metal transporter-1 (DMT-1), transferrin (Tf) and Tf-receptor-1 (TfR1), TfR-2 (TfR2) gene expression was increased. Western blot analysis of liver tissue lysate confirmed the changes observed at mRNA level. In spleen, a rapid decrease in gene expression of Fpn-1, Fpn-1a, Fpn-1b, DMT-1, Tf, TfR1 and TfR2, and an increase in hepcidin was observed. Immunohistochemistry of DMT-1 and TfR2 were mainly detected in the nucleus of rat liver and spleen, whereas TfR1 was clearly localized in the plasma membrane. Fpn-1 was mostly found in the nuclei of liver cells, whereas in spleen, the protein was mainly detected in the cell membrane. Western blot analysis of liver fractions confirmed immunohistochemical results. In livers of wild-type mice, gene expression of Fpn-1, Fpn-1a and Fpn-1b was downregulated, whereas hepcidin gene expression was increased. In contrast, these changes were less pronounced in IL-6ko-mice. Cytokine (IL-6, IL-1 beta and TNF-alpha) treatment of rat hepatocytes showed a downregulation of Fpn-1, Fpn-1a and Fpn-1b, and upregulation of hepcidin gene expression. Moreover, western blot analysis of cell lysate of IL-6-treated hepatocytes detected, as expected, an increase of alpha 2-macroglobulin (positive acute-phase protein), whereas albumin (negative acute-phase protein) and Fpn-1 were downregulated. Our results demonstrate that liver behaves as a 'sponge' for iron under acute-phase conditions, and Fpn-1 behaves as a negative acute-phase protein in rat hepatocytes mainly, but not exclusively, because of the effect of IL-6. These changes could explain iron retention in the cytoplasm and in the nucleus of hepatocytes during APR. Laboratory Investigation (2012) 92, 842-856; doi:10.1038/labinvest.2012.52; published online 2 April 2012"],["dc.description.sponsorship","Deutsche Krebshilfe [108774]"],["dc.identifier.doi","10.1038/labinvest.2012.52"],["dc.identifier.isi","000304730600004"],["dc.identifier.pmid","22469696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26353"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0023-6837"],["dc.title","Ferroportin-1 is a 'nuclear'-negative acute-phase protein in rat liver: a comparison with other iron-transport proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","125671"],["dc.bibliographiccitation.journal","BioMed Research International"],["dc.contributor.author","Abbasi, Muddasir Hassan"],["dc.contributor.author","Fatima, Sana"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Sheikh, Nadeem"],["dc.date.accessioned","2018-11-07T09:29:39Z"],["dc.date.available","2018-11-07T09:29:39Z"],["dc.date.issued","2013"],["dc.description.abstract","To gain insight into the hepatohistological alterations in noninjured rat liver, Nerium oleander (N.O.) leaves extract was injected intramuscularly to induce an acute phase reaction (APR). Histopathological changes were studied after 3, 12, and 24 h time course of sterile muscle abscess. Tissue integrity and any infiltration of inflammatory cells in the liver were investigated by Hematoxylin and Eosin and ED1 peroxidase stainings. The administration of N.O. leaves extract (10 mL/kg) in H & E stained sections showed a general vacuolization of cytoplasm resulting loss of polarity with prominent nucleoli after 3 h of induction. At 12 h, eccentric nuclei were also observed in the sections. Marked infiltration of leucocytes with predominate macrophages was also found after 24 h as seen by ED1 positive staining. In the present study, a possible relationship between serum hepcidin and total iron level was also investigated in vivo. An early increase of hepcidin and total iron level (3h) with a maximum at 12h (P < 0.01; P < 0.001) was observed. These changes indicate that sterile muscle abscess may induce APR resulting in hepatic damage which is evident with the recruitment of inflammatory cells into the organ."],["dc.identifier.doi","10.1155/2013/125671"],["dc.identifier.isi","000324179500001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31095"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Hindawi Publishing Corporation"],["dc.relation.issn","2314-6133"],["dc.title","Effect of Nerium oleander (NO) Leaves Extract on Serum hepcidin, Total Iron, and Infiltration of ED1 Positive Cells in Albino Rat"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","305"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","315"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Nischwitz, Martin"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:58:29Z"],["dc.date.available","2018-11-07T08:58:29Z"],["dc.date.issued","2011"],["dc.description.abstract","Myeloperoxidase (MPO) is involved in acute and chronic inflammatory diseases. The source of MPO in acute liver diseases is still a matter of debate. Therefore, we analysed MPO-gene expression on sections from normal and acutely damaged [carbon tetrachloride-(CCl4) or whole liver gamma-Irradiation] rat liver by immunohistochemistry, real time PCR and Western blot analysis of total RNA and protein. Also total RNA and protein from isolated Kupffer cells, hepatic stellate cells, Hepatocytes, endothelial cells and neutrophil granulocytes (NG) was analysed by real time PCR and Western blot, respectively. Sections of acutely injured human liver were prepared for MPO and CD68 immunofluorescence double staining. In normal rat liver MPO was detected immunohistochemically and by immunofluorescence double staining only in single NG. No MPO was detected in isolated parenchymal and non-parenchymal cell populations of the normal rat liver. In acutely damaged rat liver mRNA of MPO increased 2.8-fold at 24 h after administration of CCl4 and 3.3-fold at 3 h after gamma-Irradiation and MPO was detected by immunofluorescence double staining only in elastase (NE) positive NGs but not in macrophages (ED1 or CD68 positive cells). Our results demonstrate that, increased expression of MPO in damaged rat and human liver is due to recruited elastase positive NGs."],["dc.identifier.doi","10.1007/s00418-011-0787-1"],["dc.identifier.isi","000288867400007"],["dc.identifier.pmid","21327394"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6621"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23651"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Myeloperoxidase and elastase are only expressed by neutrophils in normal and in inflammed liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1801"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","American Journal Of Pathology"],["dc.bibliographiccitation.lastpage","1815"],["dc.bibliographiccitation.volume","176"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Sheikh, Nadeem"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Dudas, Jozsef"],["dc.contributor.author","Mansuroglu, Tuemen"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:44:15Z"],["dc.date.available","2018-11-07T08:44:15Z"],["dc.date.issued","2010"],["dc.description.abstract","Liver damage is a serious clinical complication of gamma-irradiation. We therefore exposed rats to single-dose gamma-irradiation (25 Gy) that was focused on the liver. Three to six hours after irradiation, an increased number of neutrophils (but not mononuclear phagocytes) was observed by immunohistochemistry to be attached to portal vessels between and around the portal (myo)fibroblasts (smooth muscle actin and Thy-1(+) cells). MCP-1/CCL2 staining was also detected in the portal vessel walls, including some cells of the portal area. CC-chemokine (MCP-1/CCL2 and MCP-3/CCL7) and CXC-chemokine (KC/CXCL1, MIP-2/CXCL2, and LIX/CXCL5) gene expression was significantly induced in total RNA from irradiated livers. In laser capture microdissected samples, an early (1 to 3 hours) up-regulation of CCL2, CXCL1, CXCL8, and CXCR2 gene expression was detected in the portal area but not in the parenchyma; with the exception of CXCL1 gene expression. In addition, treatment with an antibody against MCP-1/CCL2 before irradiation led to an increase in gene expression of interferon-gamma and IP-10/CXCL10 in liver tissue without influencing the recruitment of granulocytes. Indeed, the CCL2, CXCL1, CXCL2, and CXCL5 genes were strongly expressed and further up-regulated in liver (myo)fibroblasts after irradiation (8 Gy). Taken together, these results suggest that gamma-irradiation of the liver induces a transient accumulation of granulocytes within the portal area and that (myo)fibroblasts of the portal vessels may be one of the major sources of the chemokines involved in neutrophil recruitment. Moreover, inhibition of more than one chemokine (eg, CXCL1 and CXCL8) may be necessary to reduce leukocytes recruitment. (Am J Pathol 2010, 176:1801-1815; DOI. 10.2353/ajpath.2010.090505)"],["dc.description.sponsorship","Deutsche Krebshilfe [108774]; Bundesamt fur Strahlenschutz [StSch4546]"],["dc.identifier.doi","10.2353/ajpath.2010.090505"],["dc.identifier.isi","000276471500027"],["dc.identifier.pmid","20185578"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6274"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20155"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Investigative Pathology, Inc"],["dc.relation.issn","0002-9440"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Single-Dose Gamma-Irradiation Induces Up-Regulation of Chemokine Gene Expression and Recruitment of Granulocytes into the Portal Area but Not into Other Regions of Rat Hepatic Tissue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","520"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Shock"],["dc.bibliographiccitation.lastpage","526"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Ramadori, Guiliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:24:22Z"],["dc.date.available","2018-11-07T09:24:22Z"],["dc.date.issued","2013"],["dc.description.abstract","Ferritin L (FTL) and ferritin H (FTH) subunits are responsible for intracellular iron storage. Serum ferritin levels are not only dependant on body iron stores. Aims of the present study are to demonstrate nature, source, and major regulatory mediators of serum ferritin in an animal model of acute-phase (AP) response. Animals (rats, wild-type [WT] mice, and interleukin [IL]-6ko mice) were injected with turpentine oil (TO) intra-muscularity to induce a sterile abscess and sacrificed at different time points afterward. Rat hepatocytes were isolated for cell culture and, after reaching confluence, stimulated with major AP cytokines to induce AP conditions. We found a significantly increased expression of both ferritin subunits in liver at mRNA and protein levels during AP response. In the serum of both control and TO-injected rats, only FTL was detectable by Western blotting, whereas no increase in serum FTL was measured by Western blot or enzyme-linked immunosorbent assay. An increase in protein expression of FTL and FTH was observed in lysates of rat hepatocytes after treatment with IL-6, IL-1 beta, and tumor necrosis factor-alpha; however, only FTL was increasingly released into supernatant. In both TO-injected rats and WT mice, a dramatic increase in serum IL-6 levels was observed, along with an increased amount of hepatic ferritin subunits. However, an increase of hepatic FTL but not of FTH protein expression was observed in IL-6ko mice after TO injection. Our data demonstrate that FTL is the only rat serum ferritin whose release into circulation from the hepatocytes is increased by the effect of AP cytokines (e. g., IL-6). In contrast, FTH expression is intracellular in both under physiological and AP conditions."],["dc.description.sponsorship","Deutsche Krebshilfe [108774]"],["dc.identifier.doi","10.1097/SHK.0b013e31829266b9"],["dc.identifier.isi","000319200700009"],["dc.identifier.pmid","23524846"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29807"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1073-2322"],["dc.title","FERRITIN L IS THE SOLE SERUM FERRITIN CONSTITUENT AND A POSITIVE HEPATIC ACUTE-PHASE PROTEIN"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","353106"],["dc.bibliographiccitation.journal","BioMed Research International"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:29:26Z"],["dc.date.available","2018-11-07T09:29:26Z"],["dc.date.issued","2013"],["dc.description.abstract","The current study aimed to investigate radiation-induced regulation of iron proteins including ferritin subunits in rats. Rat livers were selectively irradiated in vivo at 25 Gy. This dose can be used to model radiation effects to the liver without inducing overt radiation-induced liver disease. Sham-irradiated rats served as controls. Isolated hepatocytes were irradiated at 8 Gy. Ferritin light polypeptide (FTL) was detectable in the serum of sham-irradiated rats with an increase after irradiation. Liver irradiation increased hepatic protein expression of both ferritin subunits. A rather early increase (3 h) was observed for hepatic TfR1 and Fpn-1 followed by a decrease at 12 h. The increase in TfR2 persisted over the observed time. Parallel to the elevation of AST levels, a significant increase (24 h) in hepatic iron content was measured. Complete blood count analysis showed a significant decrease in leukocyte number with an early increase in neutrophil granulocytes and a decrease in lymphocytes. In vitro, a significant increase in ferritin subunits at mRNA level was detected after irradiation which was further induced with a combination treatment of irradiation and acute phase cytokine. Irradiation can directly alter the expression of ferritin subunits and this response can be strongly influenced by radiation-induced proinflammatory cytokines. FTL can be used as a serum marker for early phase radiation-induced liver damage."],["dc.description.sponsorship","DFG [MA-5488/2-1]"],["dc.identifier.doi","10.1155/2013/353106"],["dc.identifier.isi","000328832300001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10734"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31028"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Hindawi Publishing Corporation"],["dc.relation.issn","2314-6141"],["dc.relation.issn","2314-6133"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Differential Regulation of Ferritin Subunits and Iron Transport Proteins: An Effect of Targeted Hepatic X-Irradiation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]