Microarray and bioinformatics analyses of gene expression profiles in BALB/c murine macrophage polarization

Abstract

Macrophages possess the hallmark feature of plasticity, allowing them to undergo a dynamic transition between M1 and M2 polarized phenotypes. The aim of the present study was to screen for differentially-expressed genes (DEGs) that were associated with BALB/c murine macrophage polarization. The transcription profiles of three M1 and three M2 samples were obtained using microarray analysis. Based on the threshold of fold-change >2.0 and P-value <0.05, a total of 1,253 DEGs were identified, of which 696 were upregulated and 557 downregulated in M1 macrophages compared with M2 macrophages. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A gene-gene interaction network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes database. GO annotation identified three categories: Cellular component, molecular function and biological process, with 34 and 40 enrichment terms consisting of upregulated and downregulated DEGs, respectively. GO enrichment analysis of DEGs was primarily associated with protein binding, response to stimulus, cell differentiation, and regulation of biological process. KEGG enrichment identified 15 and four pathways involving upregulated and downregulated DEGs, respectively. Signaling pathway analysis revealed that these DEGs were mainly involved in apoptosis, hypoxia-inducible factor (HIF) 1a pathway, innate immune system, tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction, and other signal transduction pathways. Interaction network analysis indicated that genes including TNF, interleukin (IL)-6, IL-1β, suppressor of cytokine signaling 3, nitric oxide synthase 2, HIF1a may serve key roles in macrophage polarization. The present study provided new insights into the role of genes in macrophage differentiation and polarization.