p38 kinase and c-jun N-terminal kinase oppositely regulates tumor necrosis factor α-induced vascular cell adhesion molecule-1 expression and cell adhesion in chondrosarcoma cells

We investigated signaling pathways leading to tumor necrosis factor (TNF) α-induced intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression in chondrosarcoma cells, and determined the functional significance of their expression by examining Jurkat T cell adhesion. TNF αinduced VCAM-1 and ICAM-1 expression and Jurkat T cell binding. Antibody blocking assay indicated that VCAM-1 mediates TNF α-induced Jurkat T cell adhesion. TNF αcaused activation of mitogen-activated protein (MAP) kinase subtypes, extracellular signal-regulated protein kinase, p38 kinase, and c-jun N-terminal kinase (JNK). ICAM-1 expression was not altered by the inhibition of MAP kinases. However, VCAM-1 expression and Jurkat T cell adhesion was blocked by the inhibition of p38 kinase, whereas inhibition of JNK enhanced VCAM-1 expression and cell adhesion without any modulation of NF κB activation. Our results, therefore, indicate that p38 kinase mediates TNF α-induced VCAM-1 expression and cell adhesion, whereas JNK suppresses VCAM-1 expression that is independent to NF κB activation.