Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein

It has previously been suggested that reactive oxygen species (ROS) are involved in the pathogenesis of chronic inflammatory diseases, which entails the initial activation of pro-inflammatory cytokines to facilitate leukocyte transmigration. The present study investigated whether intracellular super...

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Main Authors:	PARK, SIN-HYE, SHIN, MIN JAE, KIM, DAE WON, PARK, JINSEU, CHOI, SOO YOUNG, KANG, YOUNG-HEE
Format:	Online
Language:	English
Published:	D.A. Spandidos 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716792/

id	pubmed-4716792
recordtype	oai_dc
spelling	pubmed-47167922016-01-22 Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein PARK, SIN-HYE SHIN, MIN JAE KIM, DAE WON PARK, JINSEU CHOI, SOO YOUNG KANG, YOUNG-HEE Articles It has previously been suggested that reactive oxygen species (ROS) are involved in the pathogenesis of chronic inflammatory diseases, which entails the initial activation of pro-inflammatory cytokines to facilitate leukocyte transmigration. The present study investigated whether intracellular superoxide dismutase (SOD) suppressed monocyte endothelial trafficking and transmigration. Human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes were activated by the cytokine tumor necrosis factor-α (TNF-α) in the absence and presence of cell-permeable transactivator of transcription (Tat)-SOD protein. External stimulation with SOD was conducted using endothelial cells and monocytes. Purified cell-permeable Tat-SOD, but not non-targeted SOD, at 1–3 µM was transduced into endothelial cells in a time- and dose-dependent manner. Non-toxic Tat-SOD at ≤0.5 µM, but not 1 µM SOD, blocked the monocyte-endothelium interactions by inhibiting the TNF-α-induced stimulation of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs and integrin β1 in THP-1 cells. Endothelial VCAM-1 induction by TNF-α was responsible for superoxide anion production being quenched by N-acetyl-cysteine and Tat-SOD. SOD treatment markedly inhibited superoxide anion production induced by TNF-α, but no inhibition of endothelial transmigration was noted. Tat-SOD prevented transendothelial monocyte migration by firmly localizing occludin-1, platelet/endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial-cadherin present in paracellular junctions and inhibiting endothelial induction and activation of matrix-degrading membrane type-1 (MT-1) matrix metalloproteinase (MMP), MMP-2 and MMP-9. By contrast, treatment with 1 µM SOD did not have such effects. Furthermore, transduced Tat-SOD hindered nuclear transactivation of nuclear factor-κB (NF-κB), modulating the induction of paracellular junction proteins and matrix-degrading MMP in TNF-α-stimulated HUVECs. Transduced Tat-SOD, but not external SOD, impeded cytokine-induced endothelial adhesion and the transmigration of monocytes. Thus, we suggest that transduced Tat-SOD qualifies as an atheroprotective agent against oxidation-driven and inflammation-associated atherosclerosis. D.A. Spandidos 2016-02 2015-12-23 /pmc/articles/PMC4716792/ /pubmed/26707483 http://dx.doi.org/10.3892/ijmm.2015.2444 Text en Copyright: © Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	PARK, SIN-HYE SHIN, MIN JAE KIM, DAE WON PARK, JINSEU CHOI, SOO YOUNG KANG, YOUNG-HEE
spellingShingle	PARK, SIN-HYE SHIN, MIN JAE KIM, DAE WON PARK, JINSEU CHOI, SOO YOUNG KANG, YOUNG-HEE Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein
author_facet	PARK, SIN-HYE SHIN, MIN JAE KIM, DAE WON PARK, JINSEU CHOI, SOO YOUNG KANG, YOUNG-HEE
author_sort	PARK, SIN-HYE
title	Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein
title_short	Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein
title_full	Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein
title_fullStr	Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein
title_full_unstemmed	Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein
title_sort	blockade of monocyte-endothelial trafficking by transduced tat-superoxide dismutase protein
description	It has previously been suggested that reactive oxygen species (ROS) are involved in the pathogenesis of chronic inflammatory diseases, which entails the initial activation of pro-inflammatory cytokines to facilitate leukocyte transmigration. The present study investigated whether intracellular superoxide dismutase (SOD) suppressed monocyte endothelial trafficking and transmigration. Human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes were activated by the cytokine tumor necrosis factor-α (TNF-α) in the absence and presence of cell-permeable transactivator of transcription (Tat)-SOD protein. External stimulation with SOD was conducted using endothelial cells and monocytes. Purified cell-permeable Tat-SOD, but not non-targeted SOD, at 1–3 µM was transduced into endothelial cells in a time- and dose-dependent manner. Non-toxic Tat-SOD at ≤0.5 µM, but not 1 µM SOD, blocked the monocyte-endothelium interactions by inhibiting the TNF-α-induced stimulation of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs and integrin β1 in THP-1 cells. Endothelial VCAM-1 induction by TNF-α was responsible for superoxide anion production being quenched by N-acetyl-cysteine and Tat-SOD. SOD treatment markedly inhibited superoxide anion production induced by TNF-α, but no inhibition of endothelial transmigration was noted. Tat-SOD prevented transendothelial monocyte migration by firmly localizing occludin-1, platelet/endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial-cadherin present in paracellular junctions and inhibiting endothelial induction and activation of matrix-degrading membrane type-1 (MT-1) matrix metalloproteinase (MMP), MMP-2 and MMP-9. By contrast, treatment with 1 µM SOD did not have such effects. Furthermore, transduced Tat-SOD hindered nuclear transactivation of nuclear factor-κB (NF-κB), modulating the induction of paracellular junction proteins and matrix-degrading MMP in TNF-α-stimulated HUVECs. Transduced Tat-SOD, but not external SOD, impeded cytokine-induced endothelial adhesion and the transmigration of monocytes. Thus, we suggest that transduced Tat-SOD qualifies as an atheroprotective agent against oxidation-driven and inflammation-associated atherosclerosis.
publisher	D.A. Spandidos
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716792/
_version_	1613525208548769792

Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein

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