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Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by photodynamic therapy

Oncogene volume 23, pages 8649–8658 (2004)Cite this article

Abstract

Photodynamic therapy (PDT) is a treatment for cancer and several noncancerous proliferating cell diseases that depends on the uptake of a photosensitizing compound followed by selective irradiation with visible light. In the presence of oxygen, irradiation leads to the production of reactive oxygen species (ROS). A large production of ROS induces the death of cancer cells by apoptosis or necrosis. A small ROS production can activate various cellular pathways. Here, we show that PDT by pyropheophorbide-a methyl ester (PPME) induces the activation of nuclear factor kappa B (NF-κB) in HMEC-1 cells. NF-κB is active since it binds to the NF-κB sites of both ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) promoters and induces the transcription of several NF-κB target genes such as those of IL-6, ICAM-1, VCAM-1. In contrast, expression of ICAM-1 and VCAM-1 at the protein level was not observed, although we measured an IL-6 secretion. Using specific chemical inhibitors, we showed that the lack of ICAM-1 and VCAM-1 expression is the consequence of their degradation by lysosomal proteases. The proteasome and calpain pathways were not involved. All these observations were consistent with the fact that no adhesion of granulocytes was observed in these conditions.

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Abbreviations

PDT:

photodynamic therapy

AP-1:

activated protein 1

NF-κB:

nuclear factor kappa B

PPME:

pyropheophorbide-a methyl ester

IL:

interleukin

TNF-α:

tumour necrosis factor α

LPS:

lipopolysacharide

ROS:

reactive oxygen species

ICAM-1:

intracellular adhesion molecule 1

VCAM-1:

vascular cell adhesion molecule-1

CAMs:

cellular adhesion molecules

Ig:

immunoglobulin

MAPK:

mitogen-activating protein kinase

EGFR:

epidermal growth factor receptor

ER:

endoplasmic reticulum

MHC-I:

major histocompatibilty complex I

EMSA:

electrophoretic mobility shift assay

RIPA:

radioimmunoprecipitation assays

ELISA:

enzyme-linked immunosorbent assay

LFA-1:

leucocyte function associated Ag 1

PDTC:

pyrrolidine dithiocarbamate

GAPDH:

glyceraldehyde-3 phosphate deshydrogenase

PAF:

para-formaldehyde

BHA:

butylated hydroxyanisole

BHT:

butylated hydroxytoluene

DBT:

3,5-di-tert-butyltoluene

l.c.:

loading control

n.s.:

nonspecific

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Acknowledgements

This work was supported by grants from the Belgian National Fund for Scientific Research (Brussels, Belgium) and from the Inter-University Attraction Poles (PAI 5/12). We thank Vincent Bours (University of Liège, Belgium), Patrizia Agostinis (KULeuven, Belgium) and Albert Girotti (University of Madison, WI, USA) for helpful suggestions and discussion. Cedric Volanti is supported by the FRIA (Brussels, Belgium), Yvette Habraken and Jacques Piette are Senior Researcher and Research Director from the Belgian National Fund for Scientific Research, respectively.

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Authors and Affiliations

  1. Laboratory of Virology and Immunology, Institute of Pathology B23, University of Liège, Liège, B-4000, Belgium

    Cédric Volanti, Geoffrey Gloire, Yvette Habraken & Jacques Piette

  2. Department of Immunology and Vaccinology, B43, University of Liège, Liège, B-4000, Belgium

    Alain Vanderplasschen

  3. Department of Pathology, Institute of Pathology B23, University of Liège, Liège, B-4000, Belgium

    Nathalie Jacobs

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  1. Cédric Volanti
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Correspondence to Jacques Piette.

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Volanti, C., Gloire, G., Vanderplasschen, A. et al. Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by photodynamic therapy. Oncogene 23, 8649–8658 (2004). https://doi.org/10.1038/sj.onc.1207871

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