Differential Role of Protein Kinase C in Cytokine Induced Lymphocyte‐Endothelium Interaction In Vitro

Publisher Website
Google Scholar
Abstract
In the present study we investigated the influence of the PKC‐inhibitor GF109203X on cytokine‐ and endotoxin‐induced expression of intercellular adhesion molecule 1 (ICAM‐1) and on the adhesion of lymphocytes to cytokine‐activated endothelial cells. We found that tumour necrosis factor alpha (TNF‐α)‐ and lipopolysaccharide (LPS)‐induced ICAM‐I expression on a human endothelium‐derived cell line (EA. hy926) were unaffected by the PKC‐inhibitor and thus appeared to be independent of PKC activation. In contrast, GF109203X significantly reduced ICAM‐1 expression induced by interferon‐γ (IFN‐γ) and interleukin‐1 (IL‐1). The functional relevance of these findings was evaluated in an adhesion assay using human umbilical vein endothelial cells (HUVEC) and peripheral blood mono‐nuclear cells (PBMC). In fact, the IFN‐γ‐ and IL‐1‐induced adhesion of PBMC to cytokine treated HUVEC could be down‐regulated by the PKC‐inhibitor, whereas TNF‐α and LPS‐mediated adhesion was not affected. Additionally, the IL‐1‐driven ICAM‐1 expression on HUVEC as well as the IL‐I induced adhesion of PBMC to HUVEC was found to be TNF‐dependent, as both effects could be inhibited by an anti‐TNF‐α monoclonal antibody (MoAb) (MAK195). Based on these data on differential regulation of cytokine‐induced lymphocyte‐indothelium interactions our study supports the use of PKC‐inhibitors as additive modulators in cytokine related pathophysiological conditions.