Investigation of microRNAs in mouse macrophage responses to lipopolysaccharide-stimulation by combining gene expression with microRNA-target information

Chia-Chun Chiu, Wei-Sheng Wu

Toll-like receptors, which stimulated by pathogen-associated molecular patterns such as lipopolysaccharides (LPS), induces the releasing of many kinds of proinflammatory cytokines to activate subsequent immune responses. Plenty of studies have also indicated the importance of TLR-signalling on the avoidance of excessive inflammation, tissue repairing and the return to homeostasis after infection and tissue injury. The significance of TLR-signalling attracts many attentions on the regulatory mechanisms since several years ago. However, as newly discovered regulators, how and how many different microRNAs (miRNAs) regulate TLR-signalling pathway are still unclear. By integrating several microarray datasets and miRNA-target information datasets, we identified 431 miRNAs and 498 differentially expressed target genes in bone marrow-derived macrophages (BMDMs) with LPS-stimulation. Cooperative miRNA network were constructed by calculating targets overlap scores, and a sub-network finding algorithm was used to identify cooperative miRNA modules. Finally, 17 and 8 modules are identified in the cooperative miRNA networks composed of miRNAs up-regulate and down-regulate genes, respectively. We used gene expression data of mouse macrophage stimulated by LPS and miRNA-target information to infer the regulatory mechanism of miRNAs on LPS-induced signalling pathway. Also, our results suggest that miRNAs can be important regulators of LPS-induced innate immune response in BMDMs.