p38 kinase and c-Jun N-terminal kinase oppositely regulates tumor necrosis factor alpha-induced vascular cell adhesion molecule-1 expression and cell adhesion in chondrosarcoma cells.
We investigated signaling pathways leading to tumor necrosis factor (TNF) alpha-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. TNFalpha induced VCAM-1 and ICAM-1 expression and Jurkat T cell binding. Antibody blocking assay indicated that VCAM-1 mediates TNFalpha-induced Jurkat T cell adhesion. TNFalpha caused 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 NFkappaB activation. Our results, therefore, indicate that p38 kinase mediates TNFalpha-induced VCAM-1 expression and cell adhesion, whereas JNK suppresses VCAM-1 expression that is independent to NFkappaB activation.
Ju
Jung-Won
JW
Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, Korea.
Kim
Song-Ja
SJ
Jun
Chang-Duk
CD
Chun
Jang-Soo
JS
D015153:Blotting, Western; D002448:Cell Adhesion; D002460:Cell Line; D002813:Chondrosarcoma / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases