Calcium/calmodulin-dependent protein kinase II regulates cyclooxygenase-2 expression and prostaglandin E2 production by activating cAMP-response element-binding protein in rat peritoneal macrophages

Prostaglandin E-2 (PGE(2)) is an important inducer of inflammation, which is also closely linked to the progress of tumours. In macrophages, PGE(2) production is regulated by arachidonic acid release and cyclooxygenase-2 (COX-2) expression. In the present study, we found that COX-2 expression can be achieved by activating Ca2+/Calmodulin (CaM)-dependent protein kinase II (CaMKII) and cAMP-response element-binding protein (CREB) in rat peritoneal macrophages. Our results indicated that lipopolysaccharide and PMA could elicit the transient increase of the concentration of intracellular free calcium ions ([Ca2+](i)), which induced activation of CaMKs with the presence of CaM. The subtype of CaMKs, CaMKII, then triggered the activation of CREB, which elevated COX-2 expression and PGE(2) production in a chronological order. These results suggested that Ca2+/CaM-dependent CaMKII plays an important role in mediating COX-2 expression and PGE(2) production by activating CREB in macrophages. The study also provides more useful information to clarify the mechanism of calcium regulation of PGE(2) production, which plays an essential role in inflammation and cancers.