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Research Article

The effect of rhG-CSF on spleen transcriptome in mouse leukopenia model induced by cyclophosphamide

, , , , , & show all
Pages 114-123 | Received 07 Aug 2013, Accepted 23 Nov 2013, Published online: 10 Mar 2014
 

Abstract

Context: RhG-CSF significantly elevates the otherwise reduced numbers of leukocytes following chemotherapy. However, prior work has predominantly focused on the effect of rhG-CSF on the hematopoietic system, and few studies have focused on the immune system.

Objective: We aimed to investigate the effect of rhG-CSF on the immune system transcriptome in a mouse leukopenia model that was induced by cyclophosphamide.

Materials and methods: A cyclophosphamide leukopenia model was established in C57BL/6 mice, which were randomly divided into a normal control group (CK), a cyclophosphamide model group (CY) and a rhG-CSF treatment group (rhG-CSF). After 3 d of rhG-CSF treatment, a mouse gene expression microarray enabled evaluation of changes in the transcriptome in the mouse spleen.

Results: About 3552 differentially expressed genes occurred among the three experimental groups, of which 74.9% (2659) concentrated on three gene expression patterns. Gene ontology and pathway analysis of 2659 differential genes showed that early in treatment when leukocyte counts remained low, rhG-CSF recovered the transcription of genes that were related to DNA damage repair and metabolism of nucleotides and amino acids. By contrast, rhG-CSF inhibited the transcription of genes involved in transendothelial migration and endocytosis, and dampened the transcription of genes associated with cell proliferation as compared with the CY group.

Conclusions: Our study suggests that rhG-CSF recovered metabolism in immune cells, suppressed in vivo immune defense, and attenuated immune cell proliferation in a cyclophosphamide induced leukopenia model. Use of gene expression microarrays can macroscopically and systematically inform the mechanism of rhG-CSF on immune cells.

Acknowledgements

We gratefully acknowledge the valuable cooperation of Dai Chen (Novel Bioinformatics Co., Ltd, Shanghai, China) in analyzing microarray data.

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