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Article Open Access

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

  • Authors:
    • Sin-Hye Park
    • Min Jae Shin
    • Dae Won Kim
    • Jinseu Park
    • Soo Young Choi
    • Young-Hee Kang
  • View Affiliations / Copyright

    Affiliations: Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon 200-702, Republic of Korea, Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 200-702, Republic of Korea
    Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 387-397
    |
    Published online on: December 23, 2015
       https://doi.org/10.3892/ijmm.2015.2444
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Park S, Shin MJ, Kim DW, Park J, Choi SY and Kang Y: Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein. Int J Mol Med 37: 387-397, 2016.
APA
Park, S., Shin, M.J., Kim, D.W., Park, J., Choi, S.Y., & Kang, Y. (2016). Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein. International Journal of Molecular Medicine, 37, 387-397. https://doi.org/10.3892/ijmm.2015.2444
MLA
Park, S., Shin, M. J., Kim, D. W., Park, J., Choi, S. Y., Kang, Y."Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein". International Journal of Molecular Medicine 37.2 (2016): 387-397.
Chicago
Park, S., Shin, M. J., Kim, D. W., Park, J., Choi, S. Y., Kang, Y."Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein". International Journal of Molecular Medicine 37, no. 2 (2016): 387-397. https://doi.org/10.3892/ijmm.2015.2444
Copy and paste a formatted citation
x
Spandidos Publications style
Park S, Shin MJ, Kim DW, Park J, Choi SY and Kang Y: Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein. Int J Mol Med 37: 387-397, 2016.
APA
Park, S., Shin, M.J., Kim, D.W., Park, J., Choi, S.Y., & Kang, Y. (2016). Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein. International Journal of Molecular Medicine, 37, 387-397. https://doi.org/10.3892/ijmm.2015.2444
MLA
Park, S., Shin, M. J., Kim, D. W., Park, J., Choi, S. Y., Kang, Y."Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein". International Journal of Molecular Medicine 37.2 (2016): 387-397.
Chicago
Park, S., Shin, M. J., Kim, D. W., Park, J., Choi, S. Y., Kang, Y."Blockade of monocyte-endothelial trafficking by transduced Tat-superoxide dismutase protein". International Journal of Molecular Medicine 37, no. 2 (2016): 387-397. https://doi.org/10.3892/ijmm.2015.2444
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