Calcium/calmodulin‐dependent protein kinase II regulates cyclooxygenase‐2 expression and prostaglandin E 2 production by activating c AMP ‐response element‐binding protein in rat peritoneal macrophages

Summary 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 C a 2+ / C almodulin ( C a M )‐dependent protein kinase II ( C a MKII ) and c AMP ‐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 ([ C a 2+ ] i ), which induced activation of C a MK s with the presence of C a M . The subtype of C a MK s, C a MKII , then triggered the activation of CREB , which elevated COX ‐2 expression and PGE 2 production in a chronological order. These results suggested that C a 2+ / C a M ‐dependent C a MKII 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.