G-CSF-activated STAT3 enhances production of the chemokine MIP-2 in bone marrow neutrophils

Journal of Leukocyte Biology

Erika Ohashi and¹  Hoainam T. Nguyen-Jackson, ²  Huiyuan Zhang¹  Stephanie S. Watowich, ²  Haiyan S. Li¹ 

[1] Department of Immunology and Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA;;Department of Immunology and Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; and  The Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas, USA

关键词: chemotaxis;    transcription;    chromatin;   

DOI  :  10.1189/jlb.0312126

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophil mobilization from the bone marrow is a critical aspect of the innate immune response, enabling a rapid deployment of phagocytes to infected or inflamed tissue. The cytokine G-CSF, which is induced rapidly during infection, elicits a swift and potent mobilizing response, yet its mechanisms of action remain poorly understood. Here, we studied the role of G-CSF and its principal signal transducer STAT3 in regulating expression of the neutrophil chemoattractant MIP-2. Our studies revealed Gr-1hi mature neutrophils as major sources of Cxcl2 (MIP-2) mRNA in bone marrow and G-CSF-responsive MIP-2 protein production. Induction of Cxcl2 was regulated directly by G-CSF-activated STAT3 via interaction at a STAT consensus element in the Cxcl2 promoter. G-CSF coordinately stimulated the association of STAT3, induction of the transcriptionally active H3K4me3 modification, and recruitment of RNA Pol II at the Cxcl2 proximal promoter, as well as the promoter region of Il8rb, encoding the MIP-2 receptor. These results suggest that the G-CSF–STAT3 pathway directly regulates transcriptional events that induce neutrophil mobilization.

【 授权许可】

Unknown