Induction of FcγRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2

Fc gamma RIIA expressed on neutrophils and monocytes has a fundamental role in combating bacterial infections. In the present study, the requirement of cytosolic phospholipase A(2) (cPLA(2)) for induction of Fc gamma RIIA expression was studied in a model of cPLA(2)-deficient PLB-985 cells (PLB-D cells). Fc gamma RIIA was acquired only during differentiation of PLB but not of PLB-D cells induced by either 1,25-dihydroxyvitamin D-3, retinoic acid, or interferon gamma. Addition of prostaglandin E-2 (PGE(2)) to PLB-D cells undergoing differentiation restored the expression of Fc gamma RIIA protein, whereas addition of indomethacin to PLB cells during differentiation inhibited both the production of PGE(2) and the expression of Fc gamma RIIA. Inhibition of PKA during PLB differentiation prevented Fc gamma RIIA expression, whereas dibutyryl CAMP (dbcAMP) induced its expression in both PLB and PLB-D cells. CREB phosphorylation and CREB-CRE interaction were detected only in differentiated PLB cells and not PLB-D cells and were inhibited by indomethacin. A reported gene containing a Fc gamma RIIA gene promoter fragment with the CRE element was sufficient for CREB activation. Our results are the first to show that CREB activation is involved in up-regulation of Fc gamma RIIA expression in myeloid lineages. PGE(2) formed via cPLA(2) activates CREB through PKA and this process is dependent on development of PGE(2) receptor 4.