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p38 kinase and c-Jun N-terminal kinase oppositely regulates tumor necrosis factor alpha-induced vascular cell

Jung-Won Ju1, Song-Ja Kim, Chang-Duk Jun

  • 1Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, Korea.

IUBMB Life
|February 18, 2003
PubMed

Insights

Tumor necrosis factor alpha (TNFalpha) triggers chondrosarcoma cell adhesion via VCAM-1, mediated by p38 kinase. JNK signaling, however, suppresses VCAM-1 expression, independent of NFkappaB activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Chondrosarcoma cells express adhesion molecules like ICAM-1 and VCAM-1.
  • Tumor necrosis factor alpha (TNFalpha) influences cell adhesion in various cancers.
  • Understanding TNFalpha-induced signaling is crucial for targeting chondrosarcoma progression.

Purpose of the Study:

  • To investigate the signaling pathways regulating TNFalpha-induced ICAM-1 and VCAM-1 expression in chondrosarcoma cells.
  • To determine the functional role of ICAM-1 and VCAM-1 in T cell adhesion to chondrosarcoma cells.
  • To elucidate the involvement of MAP kinase pathways in these processes.

Main Methods:

  • Chondrosarcoma cells were treated with TNFalpha.
  • Expression of ICAM-1 and VCAM-1 was analyzed.
  • Jurkat T cell adhesion assays were performed.
  • Antibody blocking assays were utilized.
  • MAP kinase inhibitors (p38, JNK) and NFkappaB activation were assessed.

Main Results:

  • TNFalpha induced VCAM-1 and ICAM-1 expression and enhanced Jurkat T cell binding.
  • VCAM-1 was identified as the primary mediator of TNFalpha-induced T cell adhesion.
  • p38 kinase inhibition blocked VCAM-1 expression and T cell adhesion.
  • JNK inhibition enhanced VCAM-1 expression and adhesion, independent of NFkappaB.

Conclusions:

  • p38 kinase signaling is essential for TNFalpha-induced VCAM-1 expression and T cell adhesion in chondrosarcoma.
  • JNK signaling negatively regulates VCAM-1 expression and cell adhesion in a manner independent of NFkappaB.
  • These findings highlight distinct roles for MAP kinases in regulating cell adhesion molecules in chondrosarcoma.

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