Ahmad, Shakil

[["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Stehle, Thea"],["dc.contributor.author","Mustroph, Julian"],["dc.contributor.author","Knierim, Maria"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Holzamer, Andreas"],["dc.contributor.author","Hilker, Michael"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2020-12-10T14:10:25Z"],["dc.date.available","2020-12-10T14:10:25Z"],["dc.date.issued","2020"],["dc.description.abstract","Pharmacologic approaches for the treatment of atrial arrhythmias are limited due to side effects and low efficacy. Thus, the identification of new antiarrhythmic targets is of clinical interest. Recent genome studies suggested an involvement of SCN10A sodium channels (NaV1.8) in atrial electrophysiology. This study investigated the role and involvement of NaV1.8 (SCN10A) in arrhythmia generation in the human atria and in mice lacking NaV1.8. NaV1.8 mRNA and protein were detected in human atrial myocardium at a significant higher level compared to ventricular myocardium. Expression of NaV1.8 and NaV1.5 did not differ between myocardium from patients with atrial fibrillation and sinus rhythm. To determine the electrophysiological role of NaV1.8, we investigated isolated human atrial cardiomyocytes from patients with sinus rhythm stimulated with isoproterenol. Inhibition of NaV1.8 by A-803467 or PF-01247324 showed no effects on the human atrial action potential. However, we found that NaV1.8 significantly contributes to late Na+ current and consequently to an increased proarrhythmogenic diastolic sarcoplasmic reticulum Ca2+ leak in human atrial cardiomyocytes. Selective pharmacological inhibition of NaV1.8 potently reduced late Na+ current, proarrhythmic diastolic Ca2+ release, delayed afterdepolarizations as well as spontaneous action potentials. These findings could be confirmed in murine atrial cardiomyocytes from wild-type mice and also compared to SCN10A−/− mice (genetic ablation of NaV1.8). Pharmacological NaV1.8 inhibition showed no effects in SCN10A−/− mice. Importantly, in vivo experiments in SCN10A−/− mice showed that genetic ablation of NaV1.8 protects against atrial fibrillation induction. This study demonstrates that NaV1.8 is expressed in the murine and human atria and contributes to late Na+ current generation and cellular arrhythmogenesis. Blocking NaV1.8 selectively counteracts this pathomechanism and protects against atrial arrhythmias. Thus, our translational study reveals a new selective therapeutic target for treating atrial arrhythmias."],["dc.identifier.doi","10.1007/s00395-020-0780-8"],["dc.identifier.pmid","32078054"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70756"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/349"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY 4.0"],["dc.title","Inhibition of NaV1.8 prevents atrial arrhythmogenesis in human and mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1807"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","1821"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Alwahsh, Salamah Mohammad"],["dc.contributor.author","Xu, Min"],["dc.contributor.author","Seyhan, Hatice Ali"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Schultze, Frank Christian"],["dc.date.accessioned","2018-11-07T09:43:39Z"],["dc.date.available","2018-11-07T09:43:39Z"],["dc.date.issued","2014"],["dc.description.abstract","AIM: To explore lipocalin-2 (LCN-2) expression and its possible role and mechanism(s) of production in rat models of diet-inducible fatty liver. METHODS: Fatty liver was triggered in male Sprague-Dawley rats fed either with liquid Lieber-DeCarli (LDC) or LDC + 70% cal fructose (L-HFr) diet for 4 or 8 wk. Chow-nourished animals served as controls. Hepatic expression of LCN-2 and other metabolic and inflammatory mediators was assessed by quantitative reverse transcription polymerase chain reaction and Western blotting. Serum LCN-2, fasting leptin, and lipid profile were evaluated via Enzyme-Linked Immunosorbent Assay, Radioimmunoassay, and colorimetric assays, respectively. The localization of LCN-2 in the liver was detected by using immunofluorescence staining. Furthermore, HE stain was used to evaluate hepatic fat degeneration and inflammation. RESULTS: Both LDC-fed and L-HFr-fed rat histologically featured fatty liver. In the liver, mRNA transcriptions of Mcp-1, a2-m, Il-8 and Glut5 were increased in the L-HFr group at both time points (P < 0.001), while the transcription of Tlr4, Inos, and Tnf-alpha was significantly up-regulated at week 4. Interestingly, hepatic Lcn-2 expression was 90-fold at week 4 and 507-fold at week 8 higher in L-HFr-subjected rats vs control (P < 0.001). In contrast to HDL-cholesterol, systemic levels of LCN-2, fasting leptin and triglycerides were elevated in the L-HFr regimen (P < 0.001). Moreover, protein expression of hepatic LCN-2, CD14, phospho-MAPK, caspase-9, cytochrome c and 4-hydroxynonenal was increased in the L-HFr group. Conversely, the hepatic expression of PGC-1 alpha (a mitochondrial-biogenic protein) was reduced in the L-HFr category at week 8. The localization of LCN-2 in the liver was predominantly restricted to MPO+ granulocytes. CONCLUSION: Fructose diet up-regulates hepatic LCN-2 expression, which correlates with the increased indicators of oxidative stress and mitochondrial dysfunction. The LCN-2 may be involved in liver protection. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved."],["dc.description.sponsorship","Open Access Publikationsfonds 2014"],["dc.identifier.doi","10.3748/wjg.v20.i7.1807"],["dc.identifier.isi","000331966100016"],["dc.identifier.pmid","24587658"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10409"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34228"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Baishideng Publ Grp Co Ltd"],["dc.relation.issn","2219-2840"],["dc.relation.issn","1007-9327"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Diet high in fructose leads to an overexpression of lipocalin-2 in rat fatty 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.artnumber","6586"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Bengel, Philipp"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Hartmann, Nico Horst"],["dc.contributor.author","A. Mohamed, Belal"],["dc.contributor.author","Krekeler, Miriam Celine"],["dc.contributor.author","Maurer, Wiebke"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Trum, Maximilian"],["dc.contributor.author","Sossalla, Samuel Tobias"],["dc.date.accessioned","2021-12-01T09:20:52Z"],["dc.date.available","2021-12-01T09:20:52Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract An interplay between Ca 2+ /calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na + current (I NaL ) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform Na V 1.8 for CaMKIIδc-dependent proarrhythmia. In a CRISPR-Cas9-generated human iPSC-cardiomyocyte homozygous knock-out of Na V 1.8, we demonstrate that Na V 1.8 contributes to I NaL formation. In addition, we reveal a direct interaction between Na V 1.8 and CaMKIIδc in cardiomyocytes isolated from patients with heart failure (HF). Using specific blockers of Na V 1.8 and CaMKIIδc, we show that Na V 1.8-driven I NaL is CaMKIIδc-dependent and that Na V 1.8-inhibtion reduces diastolic SR-Ca 2+ leak in human failing cardiomyocytes. Moreover, increased mortality of CaMKIIδc-overexpressing HF mice is reduced when a Na V 1.8 knock-out is introduced. Cellular and in vivo experiments reveal reduced ventricular arrhythmias without changes in HF progression. Our work therefore identifies a proarrhythmic CaMKIIδc downstream target which may constitute a prognostic and antiarrhythmic strategy."],["dc.identifier.doi","10.1038/s41467-021-26690-1"],["dc.identifier.pii","26690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94290"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/412"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","Detrimental proarrhythmogenic interaction of Ca2+/calmodulin-dependent protein kinase II and NaV1.8 in heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11471"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International journal of clinical and experimental pathology"],["dc.bibliographiccitation.lastpage","11479"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Moriconi, Federico"],["dc.date.accessioned","2019-07-10T08:12:06Z"],["dc.date.available","2019-07-10T08:12:06Z"],["dc.date.issued","2017"],["dc.description.abstract","Background: The liver plays a key role in iron homeostasis during injury and hypoxia. Methods: For induction of liver injury, thioacetamide (TAA) was administered intraperitoneally to male Sprague Dawley rats. Animals were sacrificed at 0, 1, 3, 6, 12, 24, 48, 72 and 96 h. Serum, liver, spleen and heart tissues were collected from control and TAA-treated rats. Tissue sections were prepared for immunohistochemical studies. Nuclear and cytoplasmic proteins were isolated for Western blot analysis. Results: Hypoxia inducible factor (HIF)-1α and ED1 positive cells accumulated around the portal field and the interlobular space within 12 hours after TAA administration. Accordingly, Western blot analysis of liver tissue showed an early increase of HIF1α followed by a decrease at 48 h to 96 h. For Erythropoietin (EPO), as well as for HIF1- and -2α, a time-dependent translocation was observed from the cytoplasmic to the nuclear compartment. Conclusion: Our data suggest that the TAA-induced acute liver damage generates HIF-1α dependent rescue mechanisms with translocation of EPO from the cytoplasmic to the nuclear compartment. Enhanced iron transport into the liver could be necessary for increased metabolic activities during repair processes."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60864"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","1936-2625"],["dc.rights.access","openAccess"],["dc.subject","Thioacetamide (TAA); acute phase injury; hypoxia inducible factor (HIF); erythropoietin (EPO)"],["dc.subject.ddc","610"],["dc.title","Mediators of hypoxia in a rat model of sterile-induced acute liver injury"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","154"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","163"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Molina, Cristina E."],["dc.contributor.author","Tirilomis, Theodoros"],["dc.contributor.author","Kutschka, Ingo"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-26T11:03:53Z"],["dc.date.available","2019-02-26T11:03:53Z"],["dc.date.issued","2019"],["dc.description.abstract","Aims In hypertrophy and heart failure, the proarrhythmic persistent Na+ current (INaL) is enhanced. We aimed to investigate the electrophysiological role of neuronal sodium channel NaV1.8 in human hypertrophied myocardium. Methods and results Myocardial tissue of 24 patients suffering from symptomatic severe aortic stenosis and concomitant significant afterload-induced hypertrophy with preserved ejection fraction was used and compared with 12 healthy controls. We performed quantitative real-time PCR and western blot and detected a significant up-regulation of NaV1.8 mRNA (2.34fold) and protein expression (1.96-fold) in human hypertrophied myocardium compared with healthy hearts. Interestingly, NaV1.5 protein expression was significantly reduced in parallel (0.60-fold). Using whole-cell patch-clamp technique, we found that the prominent INaL was significantly reduced after addition of novel NaV1.8-specific blockers either A-803467 (30 nM) or PF-01247324 (1 μM) in human hypertrophic cardiomyocytes. This clearly demonstrates the relevant contribution of NaV1.8 to this proarrhythmic current. We observed a significant action potential duration shortening and performed confocal microscopy, demonstrating a 50% decrease in proarrhythmic diastolic sarcoplasmic reticulum (SR)-Ca2+ leak and SR-Ca2+ spark frequency after exposure to both NaV1.8 inhibitors."],["dc.identifier.doi","10.1002/ehf2.12378"],["dc.identifier.pmid","30378291"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57615"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/242"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY-NC 4.0"],["dc.title","The functional consequences of sodium channel NaV1.8 in human left ventricular hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","637"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Sultan, Sadaf"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Cameron, Silke"],["dc.date.accessioned","2018-11-07T10:14:35Z"],["dc.date.available","2018-11-07T10:14:35Z"],["dc.date.issued","2016"],["dc.description.abstract","Previously, we showed that lipocalin2 (LCN2) serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 +/- 2.3-fold) after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1 beta and TNF-beta) showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement."],["dc.description.sponsorship","Open-Access Publikationsfonds 2016"],["dc.identifier.doi","10.3390/ijms17050637"],["dc.identifier.isi","000378791400031"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13241"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40644"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Induction of Lipocalin2 in a Rat Model of Lung 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"]]

[["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"]]

[["dc.bibliographiccitation.artnumber","3891"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","19"],["dc.contributor.affiliation","Ahmad, Shakil; \t\t \r\n\t\t Department of Gastroenterology and Endocrinology, University Hospital, Georg-August University Goettingen, 37075 Goettingen, Germany, shakil.ahmad@med.uni-goettingen.de\t\t \r\n\t\t Department of Cardiology and Pneumology, University Hospital, Georg-August University Goettingen, 37075 Goettingen, Germany, shakil.ahmad@med.uni-goettingen.de"],["dc.contributor.affiliation","Ramadori, Giuliano; \t\t \r\n\t\t Department of Gastroenterology and Endocrinology, University Hospital, Georg-August University Goettingen, 37075 Goettingen, Germany, giulianoramadori@gmail.com"],["dc.contributor.affiliation","Moriconi, Federico; \t\t \r\n\t\t Department of Gastroenterology and Endocrinology, University Hospital, Georg-August University Goettingen, 37075 Goettingen, Germany, federicomoriconi@hotmail.it\t\t \r\n\t\t GastroCentro, Via Trevano 38, 6900 Lugano, Switzerland, federicomoriconi@hotmail.it"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Moriconi, Federico"],["dc.date.accessioned","2019-07-09T11:49:38Z"],["dc.date.available","2019-07-09T11:49:38Z"],["dc.date.issued","2018"],["dc.date.updated","2022-09-06T16:43:55Z"],["dc.description.abstract","Kupffer cells are professional phagocytes of the liver clearing bacteria from portal blood. Their clearance capacity, however, can be overwhelmed, transforming them into critical mediators of hepatic-injury. We investigated the consequences of selective Kupffer cell-overload by intraperitoneally administering pyrogen-free gadolinium chloride (GdCl3) or Zymosan into rats and into endotoxin-resistant mice (C3H/HeJ). The number of myeloperoxidase-positive (MPO+) cells increased at 3 h mainly around the portal vessel after both GdCl3 and Zymosan treatment. Simultaneously, GdCl3 administration reduced detectability of ED-1+ (but not ED-2) cells near the portal vessel. Serum chemokine (C-X-C motif) ligand 1 (CXCL-1), CXCL-2 and chemokine (C-C motif) ligand 2 (CCL-2) showed a peak at 3 h after both treatment regimens although at a higher extent after Zymosan administration. Accordingly, CXCL-1, CXCL-5 and CCL-2 gene expression in the liver was up-regulated after GdCl3 treatment at 3 h. After Zymosan administration a significant up-regulation of CXCL-1, CXCL-2, CXCL-10, CCL-2, CCL-3 and CCL-20 gene expression in liver at 3 h was observed. After Zymosan administration intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) gene expression was up-regulated in rat liver tissue. In C3H/HeJ mice both treatment regimens up-regulated CCL-2 and ICAM-1 gene expression after 3 h and down-regulated platelet endothelial cell adhesion molecule 1 (PECAM-1) gene expression. In conclusion, phagocytosis overload of Kupffer cells causes induction of several CXC, CC-chemokines, upregulation of “positive” adhesion molecule gene expression, down-regulation of the “negative” adhesion molecule PECAM-1 and a recruitment of neutrophil granulocytes in the portal area of the liver of treated rats and mice mainly in close contact to the liver macrophages."],["dc.identifier.doi","10.3390/ijms19123891"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15730"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59596"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Modulation of Chemokine- and Adhesion-Molecule Gene Expression and Recruitment of Neutrophil Granulocytes in Rat and Mouse Liver after a Single Gadolinium Chloride or Zymosan Treatment"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]