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730 results on '"Drexhage, Hemmo A"'

201. Altered fractalkine cleavage potentially promotes local inflammation in NOD salivary gland

Author

Wildenberg, ME (Manon Elisabeth), Van Helden - Meeuwsen, Corine, Drexhage, Hemmo, Versnel, Marjan, Wildenberg, ME (Manon Elisabeth), Van Helden - Meeuwsen, Corine, Drexhage, Hemmo, and Versnel, Marjan

Abstract

Introduction In the nonobese diabetic (NOD) mouse model of Sjogren's syndrome, lymphocytic infiltration is preceded by an accumulation of dendritic cells in the submandibular glands (SMGs). NOD mice also exhibit an increased frequency of mature, fractalkine receptor (CX3C chemokine receptor [CX3CR]1) expressing monocytes, which are considered to be precursors for tissue dendritic cells. To unravel further the role played by fractalkine-CX3CR1 interactions in the salivary gland inflammation, we studied the expression of fractalkine in NOD SMGs. Methods We studied protein expression using Western blot analysis of whole tissue lysates. Protease activity was measured in salivary gland tissue lysates using fluorimetric substrates. Digestive capacity of enzymes was determined by in vitro incubation of recombinant enzyme and fractalkine, followed by protein staining and Western blot. Results Fractalkine was detected in salivary glands of both NOD and control mice at all ages. Western blot analysis showed fractalkine cleavage with increasing age, which was more pronounced in NOD mice. This cleavage resulted in a decrease in the 31 kDa form of the protein, and the generation of an approximately 19 kDa band. Furthermore, in NOD animals older than 15 weeks, we noted the presence of a unique approximately 17 kDa fragment. This cleavage was organ specific, because it did not occur in brain or pancreas. Increased gelatinase and alpha-secretase activity were detected in NOD SMG and contributed to cleavage of the 31 kDa protein. Because aberrant cleavage products may induce autoimmunity, we studied the presence of autoantibodies against fractalkine. Indeed, NOD mice exhibited significantly more antibodies against fractalkine than did control animals. Conclusion These data indicate that aberrant proteolytic activity in the NOD SMG results in increased fractalkine cleavage and generation of a unique fractalkine fragment. This specific cleavage may contribute to autoimmunity.

Published
2008

202. Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse

Author

Wildenberg, Manon M.E., Van Helden-Meeuwsen, Cornelia C.G., Van De Merwe, Joop J.P., Moreno, Christophe, Drexhage, Hemmo H.A., Versnel, Marjan M.A., Wildenberg, Manon M.E., Van Helden-Meeuwsen, Cornelia C.G., Van De Merwe, Joop J.P., Moreno, Christophe, Drexhage, Hemmo H.A., and Versnel, Marjan M.A.

Abstract

Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary glands. In the NOD mouse, a model for this disease, the development of lymphocytic infiltrates in the salivary glands is preceded by an accumulation of dendritic cells (DC). Given the key importance of DC in regulating the immune response, we characterized the DC isolated from NOD salivary glands. These DC lacked membrane expression of CCR5, whereas DC from control salivary glands did express this molecule. The lack of expression was present already prior to the onset of lymphocytic infiltration, indicating that this was not the result of ongoing inflammation. DC from other sources in the NOD mouse also showed a decrease in CCR5 expression. The lack of CCR5 expression in the NOD salivary gland was accompanied by an increase in inflammatory chemokines. Furthermore, DC from CCR5-/- animals or DC treated with a CCR5 antagonist showed increased secretion of IL-12. Interestingly, in Sjögren's syndrome patients, CCR5 expression on circulating monocytes was decreased and correlated to increased levels of IL-12. These data indicate that CCR5 has regulatory properties and that the lack of CCR5 in NOD DC contributes to the proinflammatory environment in the salivary glands. © Society for Leukocyte Biology., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2008

209. S100B Serum Levels Predict Treatment Response in Patients with Melancholic Depression.

Author

Ambrée, Oliver, Bergink, Veerle, Grosse, Laura, Alferink, Judith, Drexhage, Hemmo A., Rothermundt, Matthias, Arolt, Volker, and Birkenhäger, Tom K.

Subjects
THERAPEUTIC use of biochemical markers, PSYCHIATRY, NEUROTROPHINS, ANTIDEPRESSANTS, VENLAFAXINE, HAMILTON Depression Inventory, REGRESSION analysis, THERAPEUTICS
Abstract

There is an ongoing search for biomarkers in psychiatry, for example, as diagnostic tools or predictors of treatment response. The neurotrophic factor S100 calcium binding protein B (S100B) has been discussed as a possible predictor of antidepressant response in patients with major depression, but also as a possible biomarker of an acute depressive state. The aim of the present study was to study the association of serum S100B levels with antidepressant treatment response and depression severity in melancholically depressed inpatients. Methods: After a wash-out period of 1 week, 40 inpatients with melancholic depression were treated with either venlafaxine or imipramine. S100B levels and Hamilton Depression Rating Scale (HAM-D) scores were assessed at baseline, after 7 weeks of treatment, and after 6 months. Results: Patients with high S100B levels at baseline showed a markedly better treatment response defined as relative reduction in HAM-D scores than those with low baseline S100B levels after 7 weeks (P = .002) and 6 months (P = .003). In linear regression models, S100B was a significant predictor for treatment response at both time points. It is of interest to note that nonresponders were detected with a predictive value of 85% and a false negative rate of 7.5%. S100B levels were not associated with depression severity and did not change with clinical improvement. Conclusions: Low S100B levels predict nonresponse to venlafaxine and imipramine with high precision. Future studies have to show which treatments are effective in patients with low levels of S100B so that this biomarker will help to reduce patients' burden of nonresponding to frequently used antidepressants. [ABSTRACT FROM AUTHOR]

Published
2016
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210. Study on inflammation-related genes and microRNAs, with special emphasis on the vascular repair factor HGF and miR-574-3p, in monocytes and serum of patients with T2D.

Author

Rojas, Lucy Baldeón, Weigelt, Karin, de Wit, Harm, Ozcan, Behiye, Van Oudenaren, Adri, Sempértegui, Fernando, Sijbrands, Eric, Grosse, Laura, van Zonneveld, Anton-Jan, Drexhage, Hemmo A., and Leenen, Pieter J. M.

Subjects
MICRORNA genetics, HEPATOCYTE growth factor, GENETICS of type 2 diabetes, PEOPLE with diabetes, INFLAMMATION, GENE expression, GENETICS
Abstract

Background: Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2D). In contrast, we found that the circulating monocytes lacked up-regulation of classical inflammatory genes (IL-1B, IL-6, and TNF) and there was even significant down-regulation of PTGS2. Notably, genes and a microRNA involved in adhesion, cell differentiation and morphology (CD9, DHRS3, PTPN7 and miR-34c-5p) were up-regulated in the T2D monocytes, suggesting a role of the anti-inflammatory cells in adhesion, vascular repair and invasion. Aim: To determine the gene expression of the vascular repair factor HGF in the circulating monocytes of patients with T2D and to investigate the relationship between HGF and the expression of the other previously tested monocyte genes and the contribution to the raised serum level of HGF. In addition, we tested the level of 6 microRNAs, which were previously found abnormal in the circulating monocytes, in the serum of the patients. Methods: A gene and microRNA expression study in monocytes and serum of 64 Ecuadorian patients with T2D (37-85 years) and 44 non-diabetic controls (32-87 years). Results: The gene expression of HGF was significantly raised in the monocytes of the patients with T2D and associated with the expression of genes involved in adhesion, cell differentiation and morphology. HGF gene expression did not correlate with the serum level of HGF. The monocyte expression of pro-inflammatory cytokine genes was also not associated with the serum levels of these cytokines. The level of miR-574-3p was significantly decreased in the serum of the patients with T2D, and correlated in expression with the decreased well-established inflammation-regulating miR-146a. The level of the microRNAs in serum did not correlate with their expression level in monocytes. Conclusion: In circulating monocytes of Ecuadorian T2D patients, the microRNA and gene expression of important inflammatory/chemotactic/motility/vascular repair factors differs from the expression in serum. While monocytes show a gene expression profile compatible with an anti-inflammatory state, serum shows a molecular profile compatible with an inflammatory state. Both compartments show molecular signs of vascular repair support, i.e. up-regulated HGF levels. [ABSTRACT FROM AUTHOR]

Published
2016
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215. Prevalence of interferon type I signature in CD14 monocytes of patients with Sjögren's syndrome and association with disease activity and BAFF gene expression

Author

Brkic, Zana, primary, Maria, Naomi I, additional, van Helden-Meeuwsen, Cornelia G, additional, van de Merwe, Joop P, additional, van Daele, Paul L, additional, Dalm, Virgil A, additional, Wildenberg, Manon E, additional, Beumer, Wouter, additional, Drexhage, Hemmo A, additional, and Versnel, Marjan A, additional

Published
2012
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220. Platelet-Derived Growth Factor-BB: A Stimulus for Cytokine Production by Orbital Fibroblasts in Graves' Ophthalmopathy

Author

van Steensel, Leendert, primary, Paridaens, Dion, additional, Dingjan, Gemma M., additional, van Daele, Paul L. A., additional, van Hagen, P. Martin, additional, Kuijpers, Robert W. A. M., additional, van den Bosch, Willem A., additional, Drexhage, Hemmo A., additional, Hooijkaas, Herbert, additional, and Dik, Willem A., additional

Published
2010
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221. Imatinib Mesylate and AMN107 Inhibit PDGF-Signaling in Orbital Fibroblasts: A Potential Treatment for Graves’ Ophthalmopathy

Author

van Steensel, Leendert, primary, Paridaens, Dion, additional, Schrijver, Benjamin, additional, Dingjan, Gemma M., additional, van Daele, Paul L. A., additional, van Hagen, P. Martin, additional, van den Bosch, Willem A., additional, Drexhage, Hemmo A., additional, Hooijkaas, Herbert, additional, and Dik, Willem A., additional

Published
2009
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222. Differentiation of Bone Marrow-Derived Endothelial Progenitor Cells Is Shifted into a Proinflammatory Phenotype by Hyperglycemia

Author

Loomans, Cindy J. M., primary, van Haperen, Rien, additional, Duijs, Jacques M., additional, Verseyden, Caroline, additional, de Crom, Rini, additional, Leenen, Pieter J. M., additional, Drexhage, Hemmo A., additional, de Boer, Hetty C., additional, de Koning, Eelco J. P., additional, Rabelink, Ton J., additional, Staal, Frank J. T., additional, and van Zonneveld, Anton Jan, additional

Published
2009
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223. Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats

Author

Voorbij, Hieronymus A.M., Jeucken, Pieter H.M., Kabel, Peter J., Haan, Meeny de, and Drexhage, Hemmo A.

Subjects
Islands of Langerhans -- Physiological aspects -- Models -- Research, Diabetes -- Physiological aspects -- Models -- Research, Lymphocytes -- Research -- Physiological aspects -- Models, Pancreatitis -- Research, Pathology, Cellular -- Research, Macrophages -- Research -- Physiological aspects -- Models, Health, Physiological aspects, Models, Research
Abstract

Dendritic Cells and Scavenger Macrophages in Pancreatic Islets of Prediabetic BB Rats Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease whose notorious pathologic feature is insulitis accompanied by destruction of [...]

Published
1989

236. Feature-expression heat maps – A new visual method to explore complex associations between two variable sets.

Author

Haarman, Bartholomeus C.M. (Benno), Riemersma-Van der Lek, Rixt F., Nolen, Willem A., Mendes, R., Drexhage, Hemmo A., and Burger, Huibert

Abstract

Introduction Existing methods such as correlation plots and cluster heat maps are insufficient in the visual exploration of multiple associations between genetics and phenotype, which is of importance to achieve a better understanding of the pathophysiology of psychiatric and other illnesses. The implementation of a combined presentation of effect size and statistical significance in a graphical method, added to the ordering of the variables based on the effect-ordered data display principle was deemed useful by the authors to facilitate in the process of recognizing meaningful patterns in these associations. Materials and methods The requirements, analyses and graphical presentation of the feature-expression heat map are described. The graphs display associations of two sets of ordered variables where a one-way direction is assumed. The associations are depicted as circles representing a combination of effect size (color) and statistical significance (radius). Results An example dataset is presented and relation to other methods, limitations, areas of application and possible future enhancements are discussed. Conclusion The feature-expression heat map is a useful graphical instrument to explore associations in complex biological systems where one-way direction is assumed, such as genotype-phenotype pathophysiological models. [ABSTRACT FROM AUTHOR]

Published
2015
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237. Monocyte activation, brain-derived neurotrophic factor ( BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.

Author

Mesman, Esther, Hillegers, Manon HJ, Ambree, Oliver, Arolt, Volker, Nolen, Willem A, and Drexhage, Hemmo A

Subjects
MONOCYTES, BRAIN-derived neurotrophic factor, BIPOLAR disorder in adolescence, NEUROCHEMISTRY, ENZYME activation, LONGITUDINAL method, PENTRAXINS, THERAPEUTICS
Abstract

Objectives There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder. Methods Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 ( PTX3), chemokine ligand 2 ( CCL2), and interleukin-1β ( IL-1β), and brain-derived neurotrophic factor ( BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls. Results During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages. Conclusions This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value. [ABSTRACT FROM AUTHOR]

Published
2015
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