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 E₂ (PGE₂) is an important inducer of inflammation, which is also closely linked to the progress of tumours. In macrophages, PGE₂ 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 PGE₂ production in a chronological order. These results suggested that Ca²⁺/CaM‐dependent CaMKII plays an important role in mediating COX‐2 expression and PGE₂ production by activating CREB in macrophages. The study also provides more useful information to clarify the mechanism of calcium regulation of PGE₂ production, which plays an essential role in inflammation and cancers.