Cell-type-specific activation of c-Jun N-terminal kinase by salicylates

J Cell Physiol. 1999 Apr;179(1):109-14. doi: 10.1002/(SICI)1097-4652(199904)179:1<109::AID-JCP13>3.0.CO;2-W.

Abstract

Salicylates inhibit signaling by tumor necrosis factor (TNF), including TNF-induced activation of mitogen-activated protein kinases (MAPKs). On the other hand, we recently showed that in normal human diploid fibroblasts sodium salicylate (NaSal) elicits activation of p38 MAPK but not activation of c-Jun N-terminal kinase (JNK). Here we show that NaSal treatment of COS-1 or HT-29 cells produced a sustained c-Jun N-terminal kinase (JNK) activation. Activation of JNK or p38 MAPK by NaSal (or aspirin) was not due to a nonspecific hyperosmotic effect because much higher molar concentrations of sorbitol or NaCl were required to produce a similar activation. Three structurally unrelated nonsteroidal antiinflammatory drugs (ibuprofen, acetaminophen, and indomethacin) failed to induce significant activation of JNK or p38 MAPK, suggesting that cyclooxygenase inhibition is not the underlying mechanism whereby salicylates induce p38 MAPK and JNK activation. Activation of JNK and p38 MAPKs may be relevant for some antiinflammatory actions of salicylates.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetaminophen / pharmacology
  • Adenocarcinoma / pathology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / classification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology*
  • COS Cells / drug effects
  • COS Cells / enzymology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Chlorocebus aethiops
  • Colonic Neoplasms / pathology
  • Cyclooxygenase Inhibitors / pharmacology
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology
  • Fibroblasts / drug effects
  • Humans
  • Hypertonic Solutions / pharmacology
  • Ibuprofen / pharmacology
  • Indomethacin / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • NF-kappa B / metabolism
  • Organ Specificity
  • Osmotic Pressure
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recombinant Fusion Proteins / pharmacology
  • Saline Solution, Hypertonic / pharmacology
  • Signal Transduction / drug effects
  • Sodium Salicylate / pharmacology*
  • Sorbitol / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Hypertonic Solutions
  • NF-kappa B
  • Proto-Oncogene Proteins c-jun
  • Recombinant Fusion Proteins
  • Saline Solution, Hypertonic
  • Tumor Necrosis Factor-alpha
  • Acetaminophen
  • Sorbitol
  • Epidermal Growth Factor
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Aspirin
  • Sodium Salicylate
  • Ibuprofen
  • Indomethacin