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Protein Kinase C Activation is Involved in Ultraviolet B Irradiation‐Induced Endothelial Cell ICAM‐1 Up‐Regulation and Lymphocyte–Endothelium Interaction In Vitro
Author(s) -
FUNK J. O.,
HOLLER E.,
KOHLHUBER F.,
UEFFING M.,
BORNKAMM G. W.,
KIND P.,
EISSNER G.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-324.x
Subject(s) - protein kinase c , icam 1 , biology , microbiology and biotechnology , intercellular adhesion molecule 1 , cytokine , intracellular , jurkat cells , endothelium , signal transduction , immunology , immune system , t cell , endocrinology
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 24 h after sublethal UVB irradiation of 10 mJ/cm 2 . While anti‐tumour necrosis factor (TNF)‐α antibodies or recombinant human interleukin (IL)‐10 did not influence this response, anti‐interferon (IFN)‐γ antibodies blocked the UVB‐induced ICAM‐1 up‐regulation. Significant induction of intracellular/membrane‐bound IFN‐γ 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‐α, 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‐γ induction in endothelial cells by UVB deserve further investigation.