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DC Field | Value | Language |
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dc.contributor.author | White S.J. | en |
dc.contributor.author | Khachigian L.M. | en |
dc.contributor.author | Hickey M.J. | en |
dc.contributor.author | Morand E.F. | en |
dc.contributor.author | Cheng Q. | en |
dc.contributor.author | Fan H. | en |
dc.contributor.author | Ngo D. | en |
dc.contributor.author | Beaulieu E. | en |
dc.contributor.author | Leung P. | en |
dc.contributor.author | Lo C.Y. | en |
dc.contributor.author | Burgess R. | en |
dc.contributor.author | Van Der Zwan Y.G. | en |
dc.date.accessioned | 2021-05-14T09:19:38Z | en |
dc.date.available | 2021-05-14T09:19:38Z | en |
dc.date.copyright | 2013 | en |
dc.date.created | 20130723 | en |
dc.date.issued | 2013-07-23 | en |
dc.identifier.citation | Journal of Immunology. 191 (1) (pp 424-433), 2013. Date of Publication: 01 Jul 2013. | en |
dc.identifier.issn | 0022-1767 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/27697 | en |
dc.description.abstract | Glucocorticoid-induced leucine zipper (GILZ) is an anti-inflammatory protein first identified in T lymphocytes. We recently observed that GILZ is highly expressed in synovial endothelial cells in rheumatoid arthritis. However, the function of GILZ in endothelial cells is unknown. To investigate the actions of GILZ in this cell type, we induced GILZ expression in HUVECs via transient transfection. GILZ overexpression significantly reduced the capacity of TNF-stimulated HUVECs to support leukocyte rolling, adhesion, and transmigration. These effects were associated with decreased expression of E-selectin, ICAM-1, CCL2, CXCL8, and IL-6. Experiments in a human microvascular endothelial cell line demonstrated that TNF-inducible NF-kappaB activity was significantly inhibited by overexpression of GILZ. Exogenous GILZ inhibited TNF-induced NF-kappaB p65 DNA binding, although this occurred in the absence of an effect on p65 nuclear translocation, indicating that the mechanism of action of exogenous GILZ in endothelial cells differs from that reported in other cell types. GILZ overexpression also inhibited TNF-induced activation of p38, ERK, and JNK MAPKs, as well as increased expression of the MAPK inhibitory phosphatase, MKP-1. In contrast, silencing endogenous GILZ in glucocorticoid-treated HUVECs did not alter their capacity to support leukocyte interactions. These data demonstrate that exogenous GILZ exerts inhibitory effects on endothelial cell adhesive function via a novel pathway involving modulation of NF-kappaB p65 DNA binding and MAPK activity. Induction of GILZ expression in endothelial cells may represent a novel therapeutic modality with the potential to inhibit inflammatory leukocyte recruitment. Copyright © 2013 by The American Association of Immunologists, Inc. | en |
dc.language | English | en |
dc.language | en | en |
dc.publisher | American Association of Immunologists (9650 Rockville Pike, Bethesda MD 20814, United States) | en |
dc.title | GILZ overexpression inhibits endothelial cell adhesive function through regulation of NF-kappaB and MAPK activity. | en |
dc.type | Article | en |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.4049/jimmunol.1202662 | en |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 23729444 [http://www.ncbi.nlm.nih.gov/pubmed/?term=23729444] | en |
dc.identifier.source | 369231171 | en |
dc.identifier.institution | (Cheng, Fan, Ngo, Beaulieu, Leung, Burgess, Hickey, Morand) Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia (Lo) Monash Micro Imaging, Monash University, Clayton, VIC 3168, Australia (Van Der Zwan, White) Centre for Reproduction and Development, Monash Institute of Medical Research, Clayton, VIC 3168, Australia (Khachigian) Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia | en |
dc.description.address | E.F. Morand, Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia. E-mail: eric.morand@monash.edu | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2013 Elsevier B.V., All rights reserved. | en |
dc.identifier.authoremail | Morand E.F.; eric.morand@monash.edu | en |
item.fulltext | No Fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
crisitem.author.dept | Rheumatology | - |
crisitem.author.dept | Centre for Inflammatory Diseases at Monash Health | - |
Appears in Collections: | Articles |
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