Submitted May 12, 2006
Accepted May 12, 2006
Induction of Fc
RIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2
Zahit Hazan-Eitan, Yacob Weinstein, Nurit Hadad, Aviva Konforty, and Rachel Levy*
Infectious Diseases Laboratory, Department of Clinical Biochemistry, Ben-Gurion University, Israel
Dept. Microbiology & Immunology, Faculty of Health Sciences, Gurion University, Israel
* Corresponding author; email: ral{at}bgu.ac.il.
Fc
RIIA 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 FcRIIA expression was studied in a model of cPLA2 deficient PLB-985 cells (PLB-D). FcRIIA was acquired only during differentiation of PLB but not of PLB-D cells induced by either 1,25 dihydroxyvitamin D3, retinoic acid or interferon . Addition of PGE2 to PLB-D cells undergoing differentiation restored the expression of FcRIIA protein while addition indomethacin to PLB cells during differentiation inhibited both the production of PGE2 and the expression of FcRIIA. Inhibition of PKA during PLB differentiation prevented FcRIIA expression while dbcAMP induced its expression in both PLB and PLB-D cells. CREB phophorylation 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 FcRIIA 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 FcRIIA expression in myeloid lineages. PGE2 formed via cPLA2, activates CREB through PKA and this process is dependent upon development of PGE2 receptor 4.
