Investigation of the interleukin (IL)-4/IL-4 receptor system in promyelocytic leukaemia PLB-985 cells during differentiation toward neutrophil-like phenotype: mechanism involved in IL-4-induced SOCS3 protein expression

The interleukin 4 (IL-4)/IL-4 receptor (IL-4R) system in promyelocytes is not well documented. Here, we used promyelocytic leukaemia PLB-985 cells differentiated with dimethylsulfoxide (PLB-985D) toward neutrophil-like phenotype to investigate the IL-4/IL-4R system. PLB-985 cells did not express CD132 (gamma c) but expressed the complete IL-4 type II receptor (IL-4R alpha and IL-13R alpha 1). Moreover, PLB-985 cells lost surface expression of IL-13R alpha 1 during differentiation, resulting in PLB-985D cells expressing only IL-4R alpha fully responsive to IL-4, as judged by activation of mitogen-activated protein (MAP) kinases and Janus kinase 1. IL-4 also increased suppressor of cytokine signalling 3 (SOCS3) protein level in the presence of the proteasome inhibitor MG132 exclusively in PLB-985D cells. As the IL-4R alpha chain has been associated with a component of the phagocyte NADPH oxidase, we used PLB-985-gp91(phox) deficient cells (mimicking chronic granulomatous disease, X-CGD), to investigate the IL-4/IL-4R system in X-CGD-D cells. IL- 4 was found to activate MAP kinases in X-CGD-D cells but did not up-regulate SOCS3, in contrast to granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and IL-6. Utilization of catalase, cycloheximide and genistein inhibitors showed that IL-4 induced SOCS3 by a mechanism dependent on a complete NADPH oxidase complex, protein synthesis and tyrosine phosphorylation, but independent of production of reactive oxygen species. We conclude that IL-4 induces cell signalling in promyelocytes expressing only IL-4R alpha.