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

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.

• Authors: He Guo, Fei Sun, Wei Huang, Zhiyi Liu, Shuqin Zhang, Qiuli Zhou, Chongyang Liang
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 36 Issue 2 Pg. 114-23 (Apr 2014) ISSN: 1532-2513 [Electronic] England
• PMID: 24611752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• Cyclophosphamide

Topics

• Animals
• Cell Proliferation (drug effects)
• Cyclophosphamide (pharmacology)
• DNA Repair (drug effects, genetics)
• Female
• Gene Expression (drug effects, genetics)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Leukocytes (drug effects)
• Leukopenia (chemically induced, genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Recombinant Proteins (pharmacology)
• Spleen (drug effects)
• Transcription, Genetic (drug effects, genetics)
• Transcriptome (drug effects, genetics)