J Van Damme

University of Leuven, Louvain, Flemish, Belgium

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Publications (520)2281.68 Total impact

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    ABSTRACT: Purpose:To investigate the expression of platelet factor-4 variant (PF-4var) in epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) and the role of PF-4var in the regulation of blood-retinal barrier (BRB) breakdown in diabetic rat retinas and human retinal microvascular endothelial cells (HRMEC). Methods:Rats were treated intravitreally with PF-4var or the anti-vascular endothelial growth factor (VEGF) agent bevacizumab on the first day after diabetes induction. BRB breakdown was assessed in vivo with fluorescein isothiocyanate (FITC)-conjugated dextran and in vitro in HRMEC by transendothelial electrical resistance and FITC-conjugated dextran cell permeability assay. Occludin, vascular endothelial (VE)-cadherin, hypoxia-inducible factor (HIF)-1α, VEGF, tumor necrosis factor (TNF)-α, receptor for advanced glycation end products (RAGE), caspase-3 levels and generation of reactive oxygen species (ROS) were assessed by Western blot, enzyme-linked immunosorbent assays or spectrophotometry. Results:In epiretinal membranes, vascular endothelial cells and stromal cells expressed PF-4var. In vitro, HRMEC produced PF-4var after stimulation with a combination of interleukin (IL)-1β and TNF-α and PF-4var inhibited VEGF-mediated hyperpermeability in HRMEC. In rats PF-4var was as potent as bevacizumab in attenuating diabetes-induced BRB breakdown. This effect was associated with upregulation of occludin and VE-cadherin and downregulation of HIF-1α, VEGF, TNF-α, RAGE and caspase-3, whereas ROS generation was not altered. Conclusions:Our findings suggest that increasing intraocular PF-4var levels early after the onset of diabetes protects against diabetes-induced BRB breakdown. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative ophthalmology & visual science 02/2015; 56(3). DOI:10.1167/iovs.14-16144 · 3.66 Impact Factor
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    ABSTRACT: Myofibroblasts expressing α-smooth muscle actin (α-SMA) are the key cellular mediator of fibrosis. Fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial-to-mesenchymal transition (EndoMT) and/or bone marrow-derived circulating fibrocytes contribute to the myofibroblast population present in PDR epiretinal membranes. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. All membranes contained neovessels expressing the endothelial cell marker CD31. CD31+ endothelial cells co-expressed the fibroblast/myofibroblast markers fibroblast-specific protein-1 (FSP-1) and α-SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP-1, α-SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co-localization of CD45 with FSP-1 and α-SMA and co-localization of CD11b with α-SMA and matrix metalloproteinase-9, demonstrating the presence of infiltrating fibrocytes. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial-cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP-1). These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR.
    Experimental Eye Research 01/2015; 132. DOI:10.1016/j.exer.2015.01.023 · 3.02 Impact Factor
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    ABSTRACT: Serum amyloid A (SAA) is an acute phase protein which is up-regulated in inflammatory diseases and chemoattracts monocytes, lymphocytes and granulocytes via its G protein-coupled receptor FPRL1/FPR2. Here, we demonstrated that the SAA1α isoform also chemoattracts monocyte-derived immature dendritic cells (DCs) in the Boyden and μ-slide chemotaxis assay and that its chemotactic activity for monocytes and DCs was indirectly mediated via rapid chemokine induction. Indeed, SAA1 induced significant amounts (≥5 ng/ml) of MIP-1α/CCL3 and IL-8/CXCL8 in monocytes and DCs in a dose-dependent manner within 3 h. However, SAA1 also directly activated monocytes and DCs for signaling and chemotaxis without chemokine interference. SAA1-induced monocyte migration was nevertheless significantly prevented (60 to 80% inhibition) in the constant presence of desensitizing exogenous MIP-1α/CCL3, neutralizing anti-MIP-1α/CCL3 antibody or a combination of CCR1 and CCR5 antagonists, indicating that this endogenously produced CC chemokine was indirectly contributing to SAA1-mediated chemotaxis. Further, anti-IL-8/CXCL8 antibody neutralized SAA1-induced monocyte migration, suggesting that endogenous IL-8/CXCL8 acted in concert with MIP-1α/CCL3. This explained why SAA1 failed to synergize with exogenously added MIP-1α/CCL3 or SDF-1α/CXCL12 in monocyte and DC chemotaxis. In addition to direct leukocyte activation, SAA1 induces a chemotactic cascade mediated by expression of cooperating chemokines to prolong leukocyte recruitment to the inflammatory site.This article is protected by copyright. All rights reserved
    European Journal of Immunology 01/2015; 45(1). DOI:10.1002/eji.201444818 · 4.52 Impact Factor
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    ABSTRACT: Chemokines, binding their various G protein-coupled receptors, lead the way for leukocytes in health and inflammation. Yet chemokine receptor expression is not limited to leukocytes. Accordingly, chemokines are remarkably pleiotropic molecules involved in a range of physiological as well as pathological processes. For example, the CXCR3 chemokine receptor is expressed on activated T lymphocytes, dendritic cells and natural killer cells, but also fibroblasts and smooth muscle, epithelial and endothelial cells. In men, these cells express either CXCR3A, its splice variant CXCR3B or a balanced combination of both. The CXCR3 ligands, activating both receptor variants, include CXCL4, CXCL4L1, CXCL9, CXCL10 and CXCL11. Upon CXCR3A activation these ELR-negative CXC chemokines mediate chemotactic and proliferative responses, for example in leukocytes. In contrast, CXCR3B induces anti-proliferative and anti-migratory effects, as exemplified by angiostatic effects on endothelial cells. Taken together, the unusual and versatile characteristics of CXCR3 and its ligands form the basis for their pertinent involvement in a myriad of diseases. In this review, we discuss the presence and function of all CXCR3 ligands in various malignant, angiogenic, infectious, inflammatory and other disorders. By extension, we have also elaborated on the potential therapeutic applicability of CXCR3 ligand administration or blockade, as well as their additional value as predictive or prognostic biomarkers. This review illustrates the multifunctional, intriguing character of the various CXCR3-binding chemokines. Copyright © 2014. Published by Elsevier Ltd.
    Cytokine & Growth Factor Reviews 11/2014; 26(3). DOI:10.1016/j.cytogfr.2014.11.009 · 6.54 Impact Factor
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    ABSTRACT: Gelatinase B/ matrix metalloproteinase-9 (MMP-9) (EC 3.4.24.35) cleaves many substrates and is produced by most cell types as a zymogen, proMMP-9, in complex with the tissue inhibitor of metalloproteinases-1 (TIMP-1). Natural proMMP-9 occurs as monomers, homomultimers, and heterocomplexes, but our knowledge about the overall structure of proMMP-9 monomers and multimers is limited. We investigated biochemical, biophysical, and functional characteristics of zymogen and activated forms of MMP-9 monomers and multimers. In contrast to a conventional notion of a dimeric nature of MMP-9 homomultimers, we demonstrate that these are reduction-sensitive trimers. Based on the information from electrophoresis, atomic force microscopy (AFM) and transmission electron microscopy (TEM), we generated a 3D structure model of the proMMP-9 trimer. Remarkably, the proMMP-9 trimers possessed a 50-fold higher affinity for TIMP-1 than the monomers. In vivo, this finding was reflected in a higher extent of TIMP-1 inhibition of angiogenesis induced by trimers versus monomers. Our results show that proMMP-9 trimers constitute a novel structural and functional entity that is differentially regulated by TIMP-1.
    Biochemical Journal 10/2014; DOI:10.1042/BJ20140418 · 4.78 Impact Factor
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    ABSTRACT: CXCL4 and CXCL4L1, platelet-derived CXC chemokines, and their carboxy-terminal peptides CXCL447-70 and CXCL4L147-70 previously displayed angiostatic and anti-tumoral activity in a melanoma model. Here, we found CXCL447-70 and CXCL4L147-70 to inhibit lymphatic endothelial cell proliferation in vitro. Furthermore, the angiostatic potential of CXCL447-70 and CXCL4L147-70 was tested against different angiogenic stimuli (FGF1, FGF2, FGF8, EGF and VEGF). Besides reducing FGF2-induced vascular endothelial cell growth, CXCL447-70 and CXCL4L147-70 efficiently counteracted EGF. Consequently, we considered their anti-tumoral potential in EGF-dependent MDA-MB-231 breast tumors. In tumor-bearing mice, CXCL447-70 reduced tumor growth better than CXCL4L147-70. In CXCL447-70-treated tumors significantly more intratumoral monocytes/macrophages and dendritic cells were present and higher expression levels of CCL5 and IFN- γ were detected by qPCR on tumor lysates. Because neither peptide was able to specifically bind CXCR3A or CXCR3B, differential glycosaminoglycan binding and direct interaction with cytokines (EGF and CCL5) might explain any differences in anti-tumoral effects. Notably, CCL5-induced monocyte chemotaxis in vitro was increased by addition of CXCL447-70 or CXCL4L147-70. Finally, CXCL447-70 and CXCL4L147-70 inhibited proliferation of MDA-MB-231 cells. Our results suggest a tumor type-dependent responsiveness to either CXCL447-70 or CXCL4L147-70 treatment, defined by anti-proliferative, angiostatic and inflammatory actions, and substantiate their therapeutic potential.
    Oncotarget 10/2014; · 6.63 Impact Factor
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    ABSTRACT: In vivo leukocyte recruitment is not fully understood and may result from interactions of chemokines with glycosaminoglycans/GAGs. We previously showed that chlorite-oxidized oxyamylose/COAM binds the neutrophil chemokine GCP-2/CXCL6. Here, mouse chemokine binding by COAM was studied systematically and binding affinities of chemokines to COAM versus GAGs were compared. COAM and heparan sulphate bound the mouse CXC chemokines KC/CXCL1, MIP-2/CXCL2, IP-10/CXCL10 and I-TAC/CXCL11 and the CC chemokine RANTES/CCL5 with affinities in the nanomolar range, whereas no binding interactions were observed for mouse MCP-1/CCL2, MIP-1α/CCL3 and MIP-1β/CCL4. The affinities of COAM-interacting chemokines were similar to or higher than those observed for heparan sulphate. Although COAM did not display chemotactic activity by itself, its co-administration with mouse GCP-2/CXCL6 and MIP-2/CXCL2 or its binding of endogenous chemokines resulted in fast and cooperative peritoneal neutrophil recruitment and in extravasation into the cremaster muscle in vivo. These local GAG mimetic features by COAM within tissues superseded systemic effects and were sufficient and applicable to reduce LPS-induced liver-specific neutrophil recruitment and activation. COAM mimics glycosaminoglycans and is a nontoxic probe for the study of leukocyte recruitment and inflammation in vivo.
    PLoS ONE 08/2014; 9(8):e104107. DOI:10.1371/journal.pone.0104107 · 3.53 Impact Factor
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    07/2014; DOI:10.4267/2042/54016
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    ABSTRACT: Outgrowth of Porphyromonas gingivalis within the inflammatory subgingival plaque is associated with periodontitis characterized by periodontal tissue destruction, loss of alveolar bone, periodontal pocket formation and eventually tooth loss. Potential virulence factors of P. gingivalis are peptidylarginine deiminase (PPAD), an enzyme modifying free or peptide-bound arginine to citrulline, and the bacterial proteases referred to as gingipains (Rgp and Kgp). Chemokines attract leukocytes during inflammation. However, posttranslational modification (PTM) of chemokines by proteases or human peptidylarginine deiminases may alter their biological activities. Since chemokine processing may be important in microbial defense mechanisms, we investigated whether PTM of chemokines occurs by P. gingivalis enzymes. Upon incubation of interleukin-8 (IL-8/CXCL8) with PPAD, only minor enzymatic citrullination was detected. In contrast, Rgp rapidly cleaved CXCL8 in vitro. Subsequently, different P. gingivalis strains were incubated with the chemokines CXCL8 or CXCL10 and their PTM were investigated. No significant CXCL8 citrullination was detected for the tested strains. Interestingly, although considerable differences in efficiency of CXCL8 degradation were observed with full cultures of various strains, similar rates of chemokine proteolysis were exerted by cell-free culture supernatants. Sequencing of CXCL8 incubated with supernatant or bacteria showed that CXCL8 is processed into its more potent 6-77 and 9-77 forms. In contrast, CXCL10 was entirely and rapidly degraded by P. gingivalis with no transient chemokine forms being observed. In conclusion, this study demonstrates PTM of CXCL8 and CXCL10 by gingipains of P. gingivalis and that strain differences may particularly affect the activity of these bacterial membrane-associated proteases.
    Infection and immunity 03/2014; 82(6). DOI:10.1128/IAI.01624-14 · 4.16 Impact Factor
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    ABSTRACT: CXC chemokines influence a variety of biological processes, such as angiogenesis, both in a physiological and pathological context. Platelet factor-4 (PF-4)/CXCL4 and its variant PF-4var/CXCL4L1 are known to favor angiostasis by inhibiting endothelial cell proliferation and chemotaxis. CXCL4L1 in particular is a potent inhibitor of angiogenesis with anti-tumoral characteristics, both through regulation of neovascularization and through attraction of activated lymphocytes. However, its underlying signaling pathways remain to be elucidated. Here, we have identified various intracellular pathways activated by CXCL4L1 in comparison with other CXCR3 ligands, including CXCL4 and interferon-γ-induced protein 10/CXCL10. Signaling experiments show involvement of the mitogen-activated protein kinase (MAPK) family in CXCR3A-transfected cells, activated lymphocytes and human microvascular endothelial cells (HMVEC). In CXCR3A transfectants, CXCL4 and CXCL4L1 activated p38 MAPK, as well as Src kinase within 30 and 5 min, respectively. Extracellular signal-regulated kinase (ERK) phosphorylation occured in activated lymphocytes, yet was inhibited in microvascular and lymphatic endothelial cells. CXCL4L1 and CXCL4 counterbalanced the angiogenic chemokine stromal cell-derived factor-1/CXCL12 in both endothelial cell types. Notably, inhibition of ERK signaling by CXCL4L1 and CXCL4 in lymphatic endothelial cells implies that these chemokines might also regulate lymphangiogenesis. Furthermore, CXCL4, CXCL4L1 and CXCL10 slightly enhanced forskolin-stimulated cAMP production in HMVEC. Finally, CXCL4, but not CXCL4L1, induced activation of p70S6 kinase within 5 min in HMVEC. Our findings confirm that the angiostatic chemokines CXCL4L1 and CXCL4 activate both CXCR3A and CXCR3B and bring new insights into the complexity of their signaling cascades.
    Angiogenesis 01/2014; 17(3). DOI:10.1007/s10456-014-9417-6 · 4.41 Impact Factor
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    ABSTRACT: The blood-brain barrier (BBB) is a specific structure that is composed of two basement membranes (BMs) and that contributes to the control of neuroinflammation. As long as the BBB is intact, extravasated leukocytes may accumulate between two BMs, generating vascular cuffs. Specific matrix metalloproteinases, MMP-2 and MMP-9, have been shown to cleave BBB beta-dystroglycan and to disintegrate thereby the parenchymal BM, resulting in encephalomyelitis. This knowledge has been added to the molecular basis of the REGA model to understand the pathogenesis of multiple sclerosis, and it gives further ground for the use of MMP inhibitors for the treatment of acute neuroinflammation. MMP-9 is associated with central nervous system inflammation and occurs in various forms: monomers and multimers. None of the various neurological and neuropathologic functions of MMP-9 have been associated with either molecular structure or molecular form, and therefore, in-depth structure-function studies are needed before medical intervention with MMP-9-specific inhibitors is initiated.
    Progress in brain research 01/2014; 214:193-206. DOI:10.1016/B978-0-444-63486-3.00009-8 · 5.10 Impact Factor
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    ABSTRACT: Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumor growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors.
    Virology 12/2013; 447(1-2):221-32. DOI:10.1016/j.virol.2013.09.019 · 3.28 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) are potent antigen presenting cells, described as the initiators of adaptive immune responses. Immature monocyte-derived DCs (MDDC) showed decreased CD14 expression, increased cell surface markers DC-SIGN and CD1a and enhanced levels of receptors for the chemokines CCL3 (CCR1/CCR5) and CXCL8 (CXCR1/CXCR2) compared with human CD14(+) monocytes. After further MDDC maturation by LPS, the markers CD80 and CD83 and the chemokine receptors CXCR4 and CCR7 were upregulated, whereas CCR1, CCR2 and CCR5 expression was reduced. CCL3 dose-dependently synergized with CXCL8 or CXCL12 in chemotaxis of immature MDDC. CXCL12 augmented the CCL3-induced ERK1/2 and Akt phosphorylation in immature MDDC, although the synergy between CCL3 and CXCL12 in chemotaxis of immature MDDC was dependent on the Akt signaling pathway but not on ERK1/2 phosphorylation. CCL2 also synergized with CXCL12 in immature MDDC migration. Moreover, two CXC chemokines not sharing receptors (CXCL12 and CXCL8) cooperated in immature MDDC chemotaxis, whereas two CC chemokines (CCL3 and CCL7) sharing CCR1 did not. Further, the non-chemokine G protein-coupled receptor ligands chemerin and fMLP synergized with respectively CCL7 and CCL3 in immature MDDC signaling and migration. Finally, CXCL12 and CCL3 did not cooperate, but CXCL12 synergized with CCL21 in mature MDDC chemotaxis. Thus, chemokine synergy in immature and mature MDDC migration is dose-dependently regulated by chemokines via alterations in their chemokine receptor expression pattern according to their role in immune responses.
    Immunobiology 10/2013; DOI:10.1016/j.imbio.2013.10.004 · 3.18 Impact Factor
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    ABSTRACT: The ESb-MP T-cell line is a highly ma- lignant murine lymphoma, which preferentially metastasizes toward the kidney. This could be a result of the local production of monocyte che- moattractant protein-1 (MCP-1) and regulated on activation, normal T expressed and secreted (RANTES), which are chemotactic for ESb-MP cells. Here, we demonstrate that ESb-MP cells are already responsive to the chemotactic activity of macrophage inflammatory protein-1 (MIP-1) and MIP-1 from 1 ng/ml onward. Moreover, upon stimulation with lipopolysaccharide (LPS) or virus, ESb-MP cells themselves produce significant amounts of MIP-1 (200 ng/ml). Indeed, the ma- jor autocrine chemoattractants, isolated from ESb-MP cells, were intact MIP-1 and MIP-1. Pretreatment with LPS or addition of MIP-1 inhib- ited the in vitro migration of ESb-MP cells toward various chemokines. Moreover, compared with un- treated lymphoma cells, LPS-treated cells pro- duced significantly less metastasis in mice. The re- sults represented here suggest that the role of che- mokines in attracting tumor cells at secondary sites depends on a balance between autocrine-produced and tissue-derived chemokines. This delicate balance should be considered in the design of an- tichemokine strategies in different tumor types. J. Leukoc. Biol. 72: 780-789; 2002.
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    ABSTRACT: Cytokines and chemokines represent two important groups of proteins that control the immune system. Dysregulation of the network in which these immunomodulators function can result in uncontrolled inflammation leading to various diseases, including rheumatoid arthritis, characterized by chronic inflammation and bone erosion. Chemokine activity is regulated at multiple levels, such as post-translational modification (PTM) of chemokines and their receptors by specific enzymes including proteases and peptidylarginine deiminases. Many in vitro experiments underscore the importance of post-translational processing of human chemokines. PTMs may enhance or reduce chemokine activity or may alter the receptor specificity of chemokine ligands. However, identification of chemokine isoforms in physiological in vivo settings forms the ultimate proof that PTM of chemokines is relevant in regulating the biological activity of these molecules. This review summarizes current knowledge on the in vivo role for PTMs in the regulation of chemokine activity.Immunology and Cell Biology advance online publication, 30 April 2013; doi:10.1038/icb.2013.16.
    Immunology and Cell Biology 04/2013; DOI:10.1038/icb.2013.16 · 4.21 Impact Factor
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    ABSTRACT: Cytokines and chemokines represent two important groups of proteins that control the human immune system. Dysregulation of the network in which these immunomodulators function can result in uncontrolled inflammation, leading to various diseases including rheumatoid arthritis (RA), characterized by chronic inflammation and bone erosion. Potential triggers of RA include autoantibodies, cytokines and chemokines. The tight regulation of cytokine and chemokine production, and biological activity is important. Tumor necrosis factor-α (TNF-α) is abundantly present in RA patients' serum and the arthritic synovium. This review, therefore, discusses first the role and regulation of the major proinflammatory cytokine TNF-α, in particular the regulation of TNF-α production, post-translational processing and signaling of TNF-α and its receptors. Owing to the important role of TNF-α in RA, the TNF-α-producing cells and the dynamics of its expression, the direct and indirect action of this cytokine and possible biological therapy for RA are described.Immunology and Cell Biology advance online publication, 30 April 2013; doi:10.1038/icb.2013.15.
    Immunology and Cell Biology 04/2013; DOI:10.1038/icb.2013.15 · 4.21 Impact Factor
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    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 04/2013; 1835(2):258. DOI:10.1016/j.bbcan.2012.08.001 · 7.58 Impact Factor
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    ABSTRACT: This study aimed at examining the presence and role of chemokines (angiogenic CCL2/MCP-1 and angiostatic CXCL4/PF-4, CXCL9/Mig, CXCL10/IP-10) in proliferative diabetic retinopathy (PDR). Regulated chemokine production in human retinal microvascular cells (HRMEC) and chemokine levels in vitreous samples from 40 PDR and 29 non-diabetic patients were analyzed. MCP-1, PF-4, Mig, IP-10 and VEGF levels in vitreous fluid from PDR patients were significantly higher than in controls. Except for IP-10, cytokine levels were significantly higher in PDR with active neovascularization and PDR without traction retinal detachment (TRD) than those in inactive PDR, PDR with TRD and control subjects. Exploratory regression analysis identified associations between higher levels of IP-10 and inactive PDR and PDR with TRD. VEGF levels correlated positively with MCP-1 and IP-10. Significant positive correlations were observed between MCP-1 and IP-10 levels. In line with these clinical findings Western blot analysis revealed increased PF-4 expression in diabetic rat retinas. HRMEC produced MCP-1, Mig and IP-10 after stimulation with IFN-γ, IL-1β or lipopolysaccharide. IFN-γ synergistically enhanced Mig and IP-10 production in response to IL-1β or lipopolysaccharide. MCP-1 was produced by HRMEC in response to VEGF treatment and activated HRMEC via the ERK and Akt/PKB pathway. On the other hand, phosphorylation of ERK induced by VEGF and MCP-1 was inhibited by PF-4, Mig and IP-10. In accordance with inhibition of angiogenic signal transduction pathways, PF-4 inhibited in vitro migration of HRMEC. Thus, regulatory roles for chemokines in PDR were demonstrated. In particular, IP-10 might be associated with the resolution of active PDR and the development of TRD.
    Experimental Eye Research 01/2013; 109. DOI:10.1016/j.exer.2013.01.008 · 3.02 Impact Factor

Publication Stats

27k Citations
2,281.68 Total Impact Points

Institutions

  • 1981–2015
    • University of Leuven
      • • Department of Microbiology and Immunology
      • • Center for Molecular and Vascular Biology
      • • Division of Forensic Biomedical Sciences
      • • Faculty of Medicine
      Louvain, Flemish, Belgium
  • 2014
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 2013–2014
    • Universitair Psychiatrisch Centrum KU Leuven
      Cortenberg, Flemish, Belgium
  • 2011
    • University of Lausanne
      Lausanne, Vaud, Switzerland
  • 1996–2011
    • Ludwig Institute for Cancer Research
      La Jolla, California, United States
    • Instytut Chemicznej Przeróbki Węgla
      Hindenburg, Silesian Voivodeship, Poland
  • 1995–2010
    • The Institute for Molecular Medicine
      Huntington Beach, California, United States
  • 2008
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 2006
    • University of Milan
      Milano, Lombardy, Italy
  • 1985–2006
    • Ghent University
      • • Department of Food Safety and Food Quality
      • • Department of Biochemistry (Medicine)
      Gand, Flanders, Belgium
  • 2005
    • Vanderbilt University
      Nashville, Michigan, United States
  • 2002
    • Vrije Universiteit Brussel
      Bruxelles, Brussels Capital, Belgium
  • 1999
    • University of Oxford
      • Department of Biochemistry
      Oxford, England, United Kingdom
  • 1998
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1996–1998
    • Beijing Medical University
      • Department of Immunology
      Peping, Beijing, China
  • 1992–1998
    • University of Antwerp
      Antwerpen, Flemish, Belgium
    • Texas A&M University
      • Department of Entomology
      College Station, Texas, United States
    • National Veterinary Laboratory
      Franklin Lakes, New Jersey, United States
  • 1997
    • King Abdulaziz University
      • Department of Ophthalmology
      Djidda, Makkah, Saudi Arabia
    • University of Nottingham
      • School of Medicine
      Nottigham, England, United Kingdom
  • 1989–1996
    • Mario Negri Institute for Pharmacological Research
      Milano, Lombardy, Italy
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 1988–1996
    • Leiden University Medical Centre
      • Department of Hematology
      Leyden, South Holland, Netherlands
    • Austrian Academy of Sciences
      • Institut für Molekulare Biotechnologie (IMBA)
      Vienna, Vienna, Austria
  • 1994
    • Saint Petersburg Medical Academy
      Sankt-Peterburg, St.-Petersburg, Russia
    • University of Texas Medical Branch at Galveston
      • Department of Internal Medicine
      Galveston, TX, United States
  • 1993
    • Utrecht University
      Utrecht, Utrecht, Netherlands
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
  • 1990–1992
    • Universitair Ziekenhuis Leuven
      • Department of General internal medicine
      Louvain, Flanders, Belgium
  • 1987–1991
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
    • Maastricht University
      • Algemene Heelkunde
      Maastricht, Provincie Limburg, Netherlands