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Knockdown of mouse VCAM-1 by vector-based siRNA.

Publication ,  Journal Article
Alam, AKMS; Florey, O; Weber, M; Pillai, RG; Chan, C; Tan, PH; Lechler, RI; McClure, MO; Haskard, DO; George, AJT
Published in: Transpl Immunol
November 2006

Graft rejection is critically dependent on the recruitment of leukocytes via adhesion molecules on the endothelium, and inhibition of these interactions can prolong graft survival. We have therefore developed an approach using siRNA to inhibit the expression of VCAM-1 in endothelial cells. We transfected siRNA constructs into murine corneal and vascular endothelium and looked at expression of VCAM-1 and other surface molecules by flow cytometry. Adhesion assays (both static and under flow) were used to determine the effect of VCAM-1 inhibition. The activation of cellular stress responses was assessed by RT-PCR. Constructs encoding siRNA can block expression of VCAM-1 in both corneal and vascular endothelial cells (in the latter case after cytokine stimulation). Inhibition of VCAM-1 expression reduced the ability of T cells to adhere to endothelium. However, there were non-specific effects of siRNA expression, including upregulation of (Programmed Death Ligand 1) PDL1 and decreased cell growth. Analysis of stress pathways showed that the endothelial cells transfected with siRNA had upregulated molecules associated with cell stress. While these data are supportive of a potential therapeutic role for siRNA constructs in blocking the expression of adhesion molecules, they also highlight potential non-specific effects of siRNA that must be carefully considered in any application of this technology.

Duke Scholars

Published In

Transpl Immunol

DOI

ISSN

0966-3274

Publication Date

November 2006

Volume

16

Issue

3-4

Start / End Page

185 / 193

Location

Netherlands

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Transfection
  • Surgery
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Oxidative Stress
  • Mice
  • Humans
  • Genetic Vectors
  • Genetic Techniques
 

Citation

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MLA
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Alam, A. K. M. S., Florey, O., Weber, M., Pillai, R. G., Chan, C., Tan, P. H., … George, A. J. T. (2006). Knockdown of mouse VCAM-1 by vector-based siRNA. Transpl Immunol, 16(3–4), 185–193. https://doi.org/10.1016/j.trim.2006.08.004
Alam, AKM Shamsul, Oliver Florey, Michele Weber, Radhakrishna G. Pillai, Cliburn Chan, Peng H. Tan, Robert I. Lechler, Myra O. McClure, Dorian O. Haskard, and Andrew J. T. George. “Knockdown of mouse VCAM-1 by vector-based siRNA.Transpl Immunol 16, no. 3–4 (November 2006): 185–93. https://doi.org/10.1016/j.trim.2006.08.004.
Alam AKMS, Florey O, Weber M, Pillai RG, Chan C, Tan PH, et al. Knockdown of mouse VCAM-1 by vector-based siRNA. Transpl Immunol. 2006 Nov;16(3–4):185–93.
Alam, AKM Shamsul, et al. “Knockdown of mouse VCAM-1 by vector-based siRNA.Transpl Immunol, vol. 16, no. 3–4, Nov. 2006, pp. 185–93. Pubmed, doi:10.1016/j.trim.2006.08.004.
Alam AKMS, Florey O, Weber M, Pillai RG, Chan C, Tan PH, Lechler RI, McClure MO, Haskard DO, George AJT. Knockdown of mouse VCAM-1 by vector-based siRNA. Transpl Immunol. 2006 Nov;16(3–4):185–193.
Journal cover image

Published In

Transpl Immunol

DOI

ISSN

0966-3274

Publication Date

November 2006

Volume

16

Issue

3-4

Start / End Page

185 / 193

Location

Netherlands

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Transfection
  • Surgery
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Oxidative Stress
  • Mice
  • Humans
  • Genetic Vectors
  • Genetic Techniques