Open Access

Aminophylline modulates the permeability of endothelial cells via the Slit2‑Robo4 pathway in lipopolysaccharide‑induced inflammation

  • Authors:
    • Qin Chen
    • Xiaoming Zhou
    • Ruonan Hou
    • Zhiliang Zhou
    • Zhiyi Wang
    • Ying Chen
    • Jie Weng
    • Junnan Xu
  • View Affiliations

  • Published online on: July 21, 2021     https://doi.org/10.3892/etm.2021.10474
  • Article Number: 1042
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis and septic shock are the main cause of mortality in intensive care units. The prevention and treatment of sepsis remains a significant challenge worldwide. The endothelial cell barrier plays a critical role in the development of sepsis. Aminophylline, a non‑selective phosphodiesterase inhibitor, has been demonstrated to reduce endothelial cell permeability. However, little is known regarding the role of aminophylline in regulating vascular permeability during sepsis, as well as the potential underlying mechanisms. In the present study, the Slit2/Robo4 signaling pathway, the downstream protein, vascular endothelial (VE)‑cadherin and endothelial cell permeability were investigated in a lipopolysaccharide (LPS)‑induced inflammation model. It was indicated that, in human umbilical vein endothelial cells (HUVECs), LPS downregulated Slit2, Robo4 and VE‑cadherin protein expression levels and, as expected, increased endothelial cell permeability in vitro during inflammation. After administration of aminophylline, the protein expression levels of Slit2, Robo4 and VE‑cadherin were upregulated and endothelial cell permeability was significantly improved. These results suggested that the permeability of endothelial cells could be mediated by VE‑cadherin via the Slit2/Robo4 signaling pathway. Aminophylline reduced endothelial permeability in a LPS‑induced inflammation model. Therefore, aminophylline may represent a promising candidate for modulating vascular permeability induced by inflammation or sepsis.

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September-2021
Volume 22 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Chen Q, Zhou X, Hou R, Zhou Z, Wang Z, Chen Y, Weng J and Xu J: Aminophylline modulates the permeability of endothelial cells via the Slit2‑Robo4 pathway in lipopolysaccharide‑induced inflammation. Exp Ther Med 22: 1042, 2021
APA
Chen, Q., Zhou, X., Hou, R., Zhou, Z., Wang, Z., Chen, Y. ... Xu, J. (2021). Aminophylline modulates the permeability of endothelial cells via the Slit2‑Robo4 pathway in lipopolysaccharide‑induced inflammation. Experimental and Therapeutic Medicine, 22, 1042. https://doi.org/10.3892/etm.2021.10474
MLA
Chen, Q., Zhou, X., Hou, R., Zhou, Z., Wang, Z., Chen, Y., Weng, J., Xu, J."Aminophylline modulates the permeability of endothelial cells via the Slit2‑Robo4 pathway in lipopolysaccharide‑induced inflammation". Experimental and Therapeutic Medicine 22.3 (2021): 1042.
Chicago
Chen, Q., Zhou, X., Hou, R., Zhou, Z., Wang, Z., Chen, Y., Weng, J., Xu, J."Aminophylline modulates the permeability of endothelial cells via the Slit2‑Robo4 pathway in lipopolysaccharide‑induced inflammation". Experimental and Therapeutic Medicine 22, no. 3 (2021): 1042. https://doi.org/10.3892/etm.2021.10474