Protein kinase C activation is involved in ultraviolet B irradiation-induced endothelial cell ICAM-1 up-regulation and lymphocyte-endothelium interaction in vitro.
Lymphocyte-endothelium interactions are pivotal steps in mediating inflammatory responses. The authors have analysed the influence of ultraviolet B (UVB) irradiation on intercellular adhesion molecule (ICAM)-1 expression on cells of the human microvascular endothelial cell line (HMEC)-1 and the intracellular signalling pathways involved. Flow cytometry revealed dose-dependent ICAM-1 up-regulation with maximum induced expression 24h after sublethal UVB irradiation of 10 mJ/cm2. While anti-tumour necrosis factor (TNF)-alpha antibodies or recombinant human interleukin (IL)-10 did not influence this response, anti-interferon (IFN)-gamma antibodies blocked the UVB-induced ICAM-1 up-regulation. Significant induction of intracellular/membrane-bound IFN-gamma was measured as early as 6 h post-UVB. Since previous work has shown a differential role of protein kinase C (PKC) in cytokine induced ICAM-1 expression, the effect of a selective bisindolylmaleimide-derived PKC-inhibitor (GF109203X) was studied. Ultraviolet B-induced ICAM-1 up-regulation was effectively blocked by the PKC-inhibitor, whereas a PKA-inhibitor was ineffective. Moreover, immunofluorescence analysis showed a radiation-induced membrane translocation of PKC-alpha, indicative of enzyme activation, in HMEC-1 cells already 30 min post-UVB. The functional relevance of the UVB-induced ICAM-1 expression and involvement of PKC in this process was demonstrated in an adhesion assay with peripheral blood mononuclear cells. In conclusion, UVB-induced ICAM-1 expression on human endothelial cells involves PKC-dependent pathways and can be prevented by a PKC-inhibitor. The use of PKC-inhibitors as additive modulators in immune reactions may bear clinical potential. The mechanisms of IFN-gamma induction in endothelial cells by UVB deserve further investigation.
Funk
J O
JO
Institut für Klinische Molekularbiologie und Tumourgenetik, Munich, Germany.
Holler
E
E
Kohlhuber
F
F
Ueffing
M
M
Bornkamm
G W
GW
Kind
P
P
Eissner
G
G
D002448:Cell Adhesion / Q000502:physiology / Q000528:radiation effects; D002450:Cell Communication / Q000502:physiology / Q000528:radiation effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D004789:Enzyme Activation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D011493:Protein Kinase C / Q000378:metabolism*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects*
D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D011493:Protein Kinase C