Modular analysis of bioinformatics demonstrates a critical role for NF-κB in macrophage activation.

To achieve the goal of identifying the gene groups that regulated macrophage activation, a total of 925 differentially expressed genes of activated macrophages were found at the intersection of the three series (GSE5099-1, GSE5099-2, and GSE18686) from the Gene Expression Omnibus (GEO) database, and a sub-network was constructed based on the protein-protein interaction (PPI) network. Four communities (K = 3) were identified from the sub-network using the CFinder software. Community 1 was considered as the gene group of interest base on the heat map. GO-BP and KEGG enrichment analysis with the DAVID software showed that the functions of the 14 genes in community 1 were mainly related to the NF-κB pathway. A network was constructed using the Cytoscape software. The diagram showed that STAT1, NFKBIA, NFKAIB, JUN, and RELA were the key genes in the regulation of macrophage activation. Among these genes, RELA (NF-κB P65) was an important member of the NF-κB family, while NFKBIA (IκBα) and NFKAIB (IκBβ) were the inhibitory factors of NF-κB. Small molecules capable of regulating these five genes were identified via the CMap software, and a network diagram was generated using the Cytoscape software to provide a reference for the development of new drugs that regulate macrophage activation.