Induction of Fc gammaRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2.
Fc gammaRIIA 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 Fc gammaRIIA expression was studied in a model of cPLA2-deficient PLB-985 cells (PLB-D cells). Fc gammaRIIA was acquired only during differentiation of PLB but not of PLB-D cells induced by either 1,25-dihydroxyvitamin D3, retinoic acid, or interferon gamma. Addition of prostaglandin E2 (PGE2) to PLB-D cells undergoing differentiation restored the expression of Fc gammaRIIA protein, whereas addition of indomethacin to PLB cells during differentiation inhibited both the production of PGE2 and the expression of Fc gammaRIIA. Inhibition of PKA during PLB differentiation prevented Fc gammaRIIA 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 Fc gammaRIIA 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 gammaRIIA expression in myeloid lineages. PGE2 formed via cPLA2 activates CREB through PKA and this process is dependent on development of PGE2 receptor 4.
Hazan-Eitan
Zahit
Z
Infectious Diseases Laboratory, Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Weinstein
Yacob
Y
Hadad
Nurit
N
Konforty
Aviva
A
Levy
Rachel
R
D015703:Antigens, CD / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D017931:DNA Primers; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D017452:Receptors, IgG / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone