title: KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation.
abstract: The vascular endothelium is a critical regulator of vascular function. Diverse stimuli such as proinflammatory cytokines and hemodynamic forces modulate endothelial phenotype and thereby impact on the development of vascular disease states. Therefore, identification of the regulatory factors that mediate the effects of these stimuli on endothelial function is of considerable interest. Transcriptional profiling studies identified the Kruppel-like factor (KLF)2 as being inhibited by the inflammatory cytokine interleukin-1beta and induced by laminar shear stress in cultured human umbilical vein endothelial cells. Overexpression of KLF2 in umbilical vein endothelial cells robustly induced endothelial nitric oxide synthase expression and total enzymatic activity. In addition, KLF2 overexpression potently inhibited the induction of vascular cell adhesion molecule-1 and endothelial adhesion molecule E-selectin in response to various proinflammatory cytokines. Consistent with these observations, in vitro flow assays demonstrate that T cell attachment and rolling are markedly attenuated in endothelial monolayers transduced with KLF2. Finally, our studies implicate recruitment by KLF2 of the transcriptional coactivator cyclic AMP response element-binding protein (CBP/p300) as a unifying mechanism for these various effects. These data implicate KLF2 as a novel regulator of endothelial activation in response to proinflammatory stimuli.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Sucharita
authors.initials: S
authors.lastname: SenBanerjee
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lin
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Atkins
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Greif
authors.forename: Ravi M
authors.initials: RM
authors.lastname: Rao
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Mark W
authors.initials: MW
authors.lastname: Feinberg
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Chen
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
authors.forename: F William
authors.initials: FW
authors.lastname: Luscinskas
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Michel
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gimbrone
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Cardeña
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013314:Stress, Mechanical; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014471:Umbilical Veins; D016335:Zinc Fingers / Q000502:physiology
chemical_list: D017931:DNA Primers; D019040:E-Selectin; D007375:Interleukin-1; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D015534:Trans-Activators; D018799:Intercellular Adhesion Molecule-1; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D005982:Glutathione Transferase