title: Regulation of the cyclooxygenase-2 system by interleukin-1beta through mitogen-activated protein kinase signaling pathways: a comparative study of human neuroglioma and neuroblastoma cells.
abstract: 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-1beta), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostaglandins. The molecular mechanisms by which IL-1beta regulates inflammatory genes such as cPLA2 and COX-2 in glial and neuronal cells are poorly understood. We have studied IL-1beta-mediated gene regulation in an established glial and neuronal human cell lines. We report that IL-1beta 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-1beta-induced PGE2 production, while only SB203580 reduced both cPLA2 and COX-2 expression. Similarly, in SKNSH neuroblastoma cells, both SB203580 and PD98059 reduced IL-1beta-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-1beta-mediated PGE2 release in both of these cell lines, with differences upstream at the level of cPLA(2)/COX-2 expression. IL-1beta-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-1beta-mediated inflammatory processes in both glia and neuronal cells may provide potential targets for therapeutic intervention for neurological disorders.
authors.affiliation: M3-104, Division of Pharmacology, 2411 Holmes, UMKC School of Medicine, University of Missouri-Kansas City, MO 64108, USA.
authors.forename: Anju S
authors.initials: AS
authors.lastname: Moolwaney
authors.forename: Orisa J
authors.initials: OJ
authors.lastname: Igwe
mesh_terms: D001921:Brain / Q000201:enzymology* / Q000276:immunology; D001925:Brain Damage, Chronic / Q000201:enzymology / Q000503:physiopathology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004660:Encephalitis / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005910:Glioma; D054513:Group IV Phospholipases A2; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009410:Nerve Degeneration / Q000201:enzymology / Q000503:physiopathology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D010741:Phospholipases A / Q000235:genetics; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D015232:Dinoprostone