Macrophage differentiation of myeloid progenitor cells in response to M-CSF is regulated by the dual-specificity phosphatase DUSP5

Journal of Leukocyte Biology

Roland P. Bourette¹  Marie-France Grasset¹  Guy Mouchiroud¹  Stéphanie Gobert-Gosse¹ 

[1] Université de Lyon, Université Lyon 1, Centre de Génétique Moléculaire et Cellulaire, CNRS UMR5534, Villeurbanne, FranceUniversité de Lyon, Université Lyon 1, Centre de Génétique Moléculaire et Cellulaire, CNRS UMR5534, Villeurbanne, FranceUniversité de Lyon, Université Lyon 1, Centre de Génétique Moléculaire et Cellulaire, CNRS UMR5534, Villeurbanne, France

关键词: hematopoiesis;    MAPK;    ERK;    MKP;    CSF-1;    granulocyte;   

DOI  :  10.1189/jlb.0309151

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

M-CSF regulates the production, survival, and function of monocytes and macrophages. The MAPKs ERK1/2 are key elements for signal integration downstream of the M-CSFR, and their sustained activation is essential for macrophage differentiation. In this study, we sought to isolate genes whose induction by M-CSF is dependent on persistent MAPK activation, thereby being possibly involved in the commitment of myeloid progenitors to macrophage differentiation. Following SSH between cDNA libraries from FD-Fms cells stimulated by M-CSF for 8 h in the presence or the absence of the MEK inhibitor U0126, we isolated DUSP5. DUSP5 expression is induced by M-CSF in various myeloid cells and acts as a specific negative-feedback regulator of ERK1/2. In FD-Fms cells that proliferate and differentiate toward macrophages in response to M-CSF, overexpression of DUSP5 increased M-CSF-dependent proliferation and strongly decreased differentiation. Similarly, overexpression of DUSP5 in the multipotent EGER-Fms cells not only significantly increased M-CSF-induced proliferation and prevented macrophage differentiation but also favored granulocytic differentiation. Altogether, experiments demonstrated that DUSP5 is implicated in M-CSF signaling and suggested that it may influence myeloid cell fate.

【 授权许可】

Unknown