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 Ca(2+) /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 ([Ca(2+) ]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 Ca(2+) /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.
Department of Biophysics, School of Physics, Nankai University, Tianjin, China; Clinic Service Program, Leidos Biomedical Research Inc., Frederick, MD, USA.
Xueyuan
X
Zhou
Junying
J
Li
Wenxiu
W
Yang
D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014162:Transfection
D002614:Chelating Agents; D020536:Enzyme Activators; D047428:Protein Kinase Inhibitors; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D015232:Dinoprostone; D002118:Calcium
cAMP-response element-binding protein; calcium; calmodulin; calmodulin-dependent kinase; cyclooxygenase-2; prostaglandin E2