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2002Ju Jung-Won; Kim Song-Ja; Jun Chang-Duk; Chun Jang-Soo
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.
IUBMB life 2002;54(5):293-9.
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.

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