IFN gamma priming is involved in the activation of arginase by oligodeoxinucleotides containing CpG motifs in murine macrophages

MIRIAM LISCOVSKY; ROMINA RANOCCHIA; CAROLINA GORLINO; DIEGO ALIGNANI; GABRIEL MORÓN; BELKYS MALETTO; MARÍA C. PISTORESI-PALENCIA

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2009 vol. 128 p. 159 - 169

0019-2805

Recognition of microbial products by macrophages mediates an inflammatory response and plays a critical role in directing the host immune response against infection. In the present work, we show for the first time that synthetic oligonucleotides containing unmethylated cytosine guanine motifs (CpG) in the presence of interferon (IFN)-γ are able to stimulate both arginase and inducible Nitric Oxide Synthase in murine macrophages. Unexpectedly, IFN-γ, a cytokine believed to be an inhibitor of arginase activity, intervenes in the activation of this enzyme. A significant increase in arginase activity was observed upon a short preincubation with IFN-γ (1 hour) and subsequent CpG stimulation. Therefore, a very interesting observation of this study is that the CpG mediated arginase activity was dependent on IFN-γ priming. The increase in arginase activity under CpG plus IFN-γ stimulation was correlated with augmented expression of the arginase II isoform. The use of pharmacological specific inhibitors revealed that arginase activity was dependent on p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK), but independent of c-Jun NH2-terminal kinase (JNK) activation. This report reveals a singular effect of the combination of CpG and IFN-γ, one of the mayor cytokines produced in response to CpG administration in vivo