Ceramide induction of COX-2 and PGE(2) in pulmonary A549 cells does not involve activation of NF-kappa B

Ceramide is generated by the hydrolysis of membrane sphingomyelin by sphing omyelinase (SMase) and is implicated in multiple signaling pathways, includ ing activation of NF-kappaB. As NF-kappaB is pivotal in the expression of n umerous genes associated with airway inflammation and asthma, the effects o f ceramide and SMase were examined in human pulmonary A549 cells. Ceramide and SMaase both induced cyclooxygenase (COX)-2 protein expression and stimu lated BOB, release. However, neither ceramide nor SMase induced NF-KB DNA-b inding, loss of I kappaB alpha, or NF-kappaB-dependent transcription. Both ceramide and SMase were efficient inducers of the extracellular regulated k inase (ERK), but not Jun N-terminal kinase (JNK) or p38 mitogen-activated p rotein kinase, Since ERK is implicated in arachidonic acid availability, th ese data partly explain the ability of ceramide to induce PGE(2) release. H owever, as ERK is not required for IL-1 beta -dependent induction of COX-2, the mechanism of ceramide and SMase induction of COX-2 remains unclear. (C ) 2000 Academic Press.