Regulation of the cyclooxygenase-2 system by interleukin-1β through mitogen-activated protein kinase signaling pathways: A comparative study of human neuroglioma and neuroblastoma cells

Glial activation and inflammation following brain injury may initiate and maintain the process of neurodegeneration. Both glia and neurons synthesize proinflammatory mediators such as interleukin 1 beta (IL-1β), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostaglandins. The molecular mechanisms by which IL-1β regulates inflammatory genes such as cPLA2 and COX-2 in glial and neuronal cells are poorly understood. We have studied IL-1β-mediated gene regulation in an established glial and neuronal human cell lines. We report that IL-1β induced cPLA2 and COX-2 mRNA and protein expression and subsequent prostaglandin E2 (PGE2) release in a time-dependent manner in H4 neuroglioma cells. Both SB203580 and PD98059 [p38 and p42/44 mitogen-activated protein kinase (MAPKs) inhibitors, respectively] reduced IL-1β-induced PGE2 production, while only SB203580 reduced both cPLA2 and COX-2 expression. Similarly, in SKNSH neuroblastoma cells, both SB203580 and PD98059 reduced IL-1β-induced PGE2 release, with no detectable COX-2 and cPLA2 protein expression in these cells. Our results indicate that the signaling mechanisms of p38 and p42/44 MAPKs play a role in IL-1β-mediated PGE2 release in both of these cell lines, with differences upstream at the level of cPLA2/COX-2 expression. IL-1β-induced cPLA2 and COX-2 gene expression is modulated through the p38 MAPK pathway in both neuroglioma and neuroblastoma cells. Understanding the signaling mechanisms involved in IL-1β-mediated inflammatory processes in both glia and neuronal cells may provide potential targets for therapeutic intervention for neurological disorders.