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

Salicylates inhibit signaling by tumor necrosis factor (TNF), including TNF -induced activation of mitogen-activated protein kinases (MAPKs). On the ot her hand, we recently showed that in normal human diploid fibroblasts sodiu m 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 nonsp ecific hyperosmotic effect because much higher molar concentrations of sorb itol or NaCl were required to produce a similar activation. Three structura lly unrelated nonsteroidal antiinflammatory drugs (ibuprofen, acetaminophen , and indomethacin) failed to induce significant activation of JNK or p38 M APK, suggesting that cyclooxygenase inhibition is not the underlying mechan ism whereby salicylates induce p38 MAPK and JNK activation. Activation of I NK and p38 MAPKs may be relevant for some antiinflammatory actions of salic ylates. J. Cell. Physiol. 179:109-114, 1999. (C) 1999 Wiley-Liss, Inc.