Adenovirus-mediated expression of a mutant IkappaB kinase 2 inhibits the response of endothelial cells to inflammatory stimuli - PubMed (original) (raw)
. 2001 Mar 15;97(6):1611-7.
doi: 10.1182/blood.v97.6.1611.
Affiliations
- PMID: 11238099
- DOI: 10.1182/blood.v97.6.1611
Free article
Adenovirus-mediated expression of a mutant IkappaB kinase 2 inhibits the response of endothelial cells to inflammatory stimuli
W Oitzinger et al. Blood. 2001.
Free article
Abstract
In a variety of cell types, the transcription factor nuclear factor kappaB (NF-kappaB) functions as a mediator of stress and immune responses. In endothelial cells (ECs), it controls the expression of genes encoding, eg, cytokines, cell adhesion molecules, and procoagulatory proteins. This study investigates the effect of NF-kappaB suppression on several pathophysiologic functions of ECs, including inflammation, coagulation, and angiogenesis. A recombinant adenovirus was generated for expression of a dominant negative (dn) mutant of IkappaB kinase 2 (IKK2), a kinase that acts as an upstream activator of NF-kappaB. dnIKK2 inhibited NF-kappaB, resulting in strongly reduced nuclear translocation and DNA binding activity of the transcription factor and lack of expression of several proinflammatory markers, including E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and interleukin-8. Concomitantly, inhibition of leukocyte binding to dnIKK2-expressing ECs could be demonstrated in a cell adhesion assay. Furthermore, expression of tissue factor as well as the ability to form capillary tubes in a matrigel assay was impaired in dnIKK2-expressing ECs. These data demonstrate that NF-kappaB is of central importance not only for the inflammatory response but also for a number of other EC functions. Therefore, this transcription factor as well as its upstream regulatory signaling molecules may represent favorable targets for therapeutic interference.
Similar articles
- Activation of NF-kappa B via the Ikappa B kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells.
Denk A, Goebeler M, Schmid S, Berberich I, Ritz O, Lindemann D, Ludwig S, Wirth T. Denk A, et al. J Biol Chem. 2001 Jul 27;276(30):28451-8. doi: 10.1074/jbc.M102698200. Epub 2001 May 3. J Biol Chem. 2001. PMID: 11337506 - NF-kappa B regulation by I kappa B kinase-2 in rheumatoid arthritis synoviocytes.
Aupperle K, Bennett B, Han Z, Boyle D, Manning A, Firestein G. Aupperle K, et al. J Immunol. 2001 Feb 15;166(4):2705-11. doi: 10.4049/jimmunol.166.4.2705. J Immunol. 2001. PMID: 11160335 - Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells.
Hattori Y, Suzuki K, Hattori S, Kasai K. Hattori Y, et al. Hypertension. 2006 Jun;47(6):1183-8. doi: 10.1161/01.HYP.0000221429.94591.72. Epub 2006 Apr 24. Hypertension. 2006. PMID: 16636195 - Regulation and function of IKK and IKK-related kinases.
Häcker H, Karin M. Häcker H, et al. Sci STKE. 2006 Oct 17;2006(357):re13. doi: 10.1126/stke.3572006re13. Sci STKE. 2006. PMID: 17047224 Review.
Cited by
- Rho-Associated Coiled-Coil Kinase (ROCK) in Molecular Regulation of Angiogenesis.
Liu J, Wada Y, Katsura M, Tozawa H, Erwin N, Kapron CM, Bao G, Liu J. Liu J, et al. Theranostics. 2018 Nov 26;8(21):6053-6069. doi: 10.7150/thno.30305. eCollection 2018. Theranostics. 2018. PMID: 30613282 Free PMC article. Review. - Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy: latest evidence and clinical considerations.
Taghavi Y, Hassanshahi G, Kounis NG, Koniari I, Khorramdelazad H. Taghavi Y, et al. J Cell Commun Signal. 2019 Dec;13(4):451-462. doi: 10.1007/s12079-018-00500-8. Epub 2019 Jan 3. J Cell Commun Signal. 2019. PMID: 30607767 Free PMC article. - p75(NTR)-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte-endothelial crosstalk in diabetes after limb ischaemia.
Caporali A, Meloni M, Nailor A, Mitić T, Shantikumar S, Riu F, Sala-Newby GB, Rose L, Besnier M, Katare R, Voellenkle C, Verkade P, Martelli F, Madeddu P, Emanueli C. Caporali A, et al. Nat Commun. 2015 Aug 13;6:8024. doi: 10.1038/ncomms9024. Nat Commun. 2015. PMID: 26268439 Free PMC article. - IKK is a therapeutic target in KRAS-Induced lung cancer with disrupted p53 activity.
Bassères DS, Ebbs A, Cogswell PC, Baldwin AS. Bassères DS, et al. Genes Cancer. 2014 Apr;5(1-2):41-55. doi: 10.18632/genesandcancer.5. Genes Cancer. 2014. PMID: 24955217 Free PMC article. - MEOX2 regulates nuclear factor-kappaB activity in vascular endothelial cells through interactions with p65 and IkappaBbeta.
Chen Y, Rabson AB, Gorski DH. Chen Y, et al. Cardiovasc Res. 2010 Sep 1;87(4):723-31. doi: 10.1093/cvr/cvq117. Epub 2010 Apr 26. Cardiovasc Res. 2010. PMID: 20421348 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous