Premium
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
Author(s) -
Ratthé Claude,
Girard Denis
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06886.x
Subject(s) - interleukin 3 , biology , granulocyte colony stimulating factor receptor , microbiology and biotechnology , chemistry , stem cell , il 2 receptor , cytotoxic t cell , biochemistry , haematopoiesis , in vitro
Summary 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 (γc) but expressed the complete IL‐4 type II receptor (IL‐4Rα and IL‐13Rα1). Moreover, PLB‐985 cells lost surface expression of IL‐13Rα1 during differentiation, resulting in PLB‐985D cells expressing only IL‐4Rα 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‐4Rα 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‐4Rα.