Enhanced expression of cyclooxygenase-2 and prostaglandin E 2 in response to endotoxin after trauma is dependent on MAPK and NF-κB mechanisms

• Published in: Cellular immunology Vol. 232; no. 1; pp. 116 - 126
• Main Authors: Yan, Zhaoping, Stapleton, Philip P., Freeman, Tracy A., Fuortes, Michele, Daly, John M.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2004
• Subjects: c-jun N-terminal kinase; COX-2; Extracellular signal-regulated kinase; Macrophage; Mitogen-activated protein kinase; N-2-(Cyclohexyloxy-4-nitrophenyl)methanesulfonamide; Nuclear factor kappa B; Prostaglandin E 2; Signal transduction; Trauma; Signal transduction; COX-2; N-2-(Cyclohexyloxy-4-nitrophenyl)methanesulfonamide; Mitogen-activated protein kinase; Extracellular signal-regulated kinase; Trauma; Prostaglandin E 2; c-jun N-terminal kinase; Macrophage; Nuclear factor kappa B
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2005.03.001

Macrophage prostaglandin E
2 (PGE
2) production is important in cellular immune suppression and in affecting the potential development of sepsis after trauma. We hypothesized that macrophage PGE
2 production after trauma is regulated by mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). Mice were subjected to trauma and splenic macrophages isolated 7 days later. Macrophages from traumatized mice showed increased cyclooxygenase-2 (COX-2) mRNA, protein expression, and PGE
2 production compared with controls. Increased phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 kinase was observed in macrophages from traumatized mice. Pharmacologic inhibition of MAPK blocked trauma-induced COX-2 expression, and PGE
2 production. Trauma macrophages showed increased IκBα phosphorylation and NF-κB binding to DNA. Inhibiting IκBα blocked trauma-induced NF-κB activity, COX-2 expression and PGE
2 production. This suggests that trauma-induced PGE
2 production is mediated through MAPK and NF-κB activation and offers potential for modifying the macrophages’ responses following injury.