title: 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.
abstract: 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 (gammac) but expressed the complete IL-4 type II receptor (IL-4Ralpha and IL-13Ralpha1). Moreover, PLB-985 cells lost surface expression of IL-13Ralpha1 during differentiation, resulting in PLB-985D cells expressing only IL-4Ralpha 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-4Ralpha 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-4Ralpha.
authors.affiliation: INRS-Institut Armand-Frappier, Université du Québec, Pointe-Claire, QC, Canada.
authors.forename: Claude
authors.initials: C
authors.lastname: Ratthé
authors.forename: Denis
authors.initials: D
authors.lastname: Girard
mesh_terms: D002450:Cell Communication / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000172:deficiency; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010766:Phosphorylation; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D019948:Receptors, Interleukin-4; D050826:Suppressor of Cytokine Signaling Proteins; D015847:Interleukin-4; D014443:Tyrosine; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D053613:Janus Kinase 1; D004121:Dimethyl Sulfoxide