Signaling mechanisms involved in the activation of arachidonic acid metabolism in human astrocytoma cells by Tumor necrosis factor-α : Phosphorylation of cytosolic phospholipase A2 and transactivation of cyclooxygenase-2

摘要: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that elicits cell responses by activating the mitogen-activated protein kinase (MAP kinase) cascade and transcription factors such as nuclear factor-kappaB (NF-kappaB). As these elements play central role in mechanisms of signaling involved activation cytosolic phospholipase A2 (cPLA2) cyclooxygenase-2 (COX-2), effect TNF-alpha on arachidonate (AA) metabolism 1321N1 astrocytoma cells was assayed. produced phosphorylation cPLA2, which preceded an both c-Jun N-terminal (JNK) p38-MAP kinase, this associated with release [3H]AA. In contrast, did not activate extracellular signal-regulated p42, nor it elicit mitogenic response. Analysis [3H]AA metabolites reverse-phase HPLC showed all released during first hour after addition eluted authentic AA, whereas samples obtained at 24 h TNF-alpha, 25% had been converted into COX products compared only 9% control cells. keeping findings, increase COX-2 expression, judged from RT-PCR studies immunoblot protein, long-lasting NF-kappaB. These data show produces early JNK, followed cPLA2 AA. On other hand, NF-kappaB may explain induction expression delayed generation prostanoids.