Downregulation of ICAM-1 and VCAM-1 expression in endothelial cells treated by photodynamic therapy.
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-kappaB) in HMEC-1 cells. NF-kappaB is active since it binds to the NF-kappaB sites of both ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) promoters and induces the transcription of several NF-kappaB 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.
Laboratory of Virology and Immunology, Institute of Pathology B23, University of Liège, B-4000 Liège, Belgium.
Cédric
C
Volanti
Geoffrey
G
Gloire
Alain
A
Vanderplasschen
Nathalie
N
Jacobs
Yvette
Y
Habraken
Jacques
J
Piette
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology; D011485:Protein Binding; D014158:Transcription, Genetic / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D015850:Interleukin-6; D016328:NF-kappa B; D011166:Porphyrins; D019010:Vascular Cell Adhesion Molecule-1; C452939:pyropheophorbide-a methylester; D018799:Intercellular Adhesion Molecule-1