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

FcγRIIA expressed on neutrophils and monocytes has a fundamental role in combating bacterial infections. In the present study, the requirement of cytosolic phospholipase A₂ (cPLA₂) for induction of FcγRIIA expression was studied in a model of cPLA₂-deficient PLB-985 cells (PLB-D cells). FcγRIIA was acquired only during differentiation of PLB but not of PLB-D cells induced by either 1,25-dihydroxyvitamin D₃, retinoic acid, or interferon γ. Addition of prostaglandin E₂ (PGE₂) to PLB-D cells undergoing differentiation restored the expression of FcγRIIA protein, whereas addition of indomethacin to PLB cells during differentiation inhibited both the production of PGE₂ and the expression of FcγRIIA. Inhibition of PKA during PLB differentiation prevented FcγRIIA 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 reporter gene containing a FcγRIIA 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 FcγRIIA expression in myeloid lineages. PGE₂ formed via cPLA₂ activates CREB through PKA and this process is dependent on development of PGE₂ receptor 4.