Differences in Lipopolysaccharides-Induced Inflammatory Response Between Mouse Embryonic Fibroblasts and Bone Marrow-Derived Macrophages.

Abstract

Mouse embryonic fibroblasts (MEFs) are commonly used in research on the molecular mechanism(s) of inflammation because of its good response to inflammatory stimuli. However, the difference in inflammatory reaction between MEFs and macrophages, a classical inflammatory cell type, has not been identified. In this study, we report that both mRNA and protein levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in MEFs upon lipopolysaccharides (LPS) stimulation were significantly lower than those in bone marrow-derived macrophages (BMDMs). MAPK, NF-κB, and IRF3 pathways control the expression and production of inflammatory activated in LPS-stimulated MEFs, but showed different activation patterns in comparison with LPS-stimulated BMDMs. Upon LPS stimulation, activation of the MAPK pathway was slow and remarkably weaker in MEFs than that in BMDMs, whereas more pronounced activation of both NF-κB and IRF3 pathways was observed in MEFs compared to BMDMs. This difference in the activation of MAPK, NF-κB, and IRF3 pathways may result in different production of IL-6 and TNF-α between MEFs and BMDMs. We further revealed that substantial differences in more additional inflammatory response-related cytokines exist between LPS-stimulated MEFs and BMDMs. In conclusion, MEFs exhibit good responsiveness to LPS as a target cell for inflammation-related research. However, MEFs cannot replace macrophages because of substantial differences in their inflammatory reactivity.