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Epigenomic and transcriptomic differences between low-grade and acute inflammation in LPS-induced murine immune cells

ABSTRACT: Chronic, low-grade inflammation has a widespread and significant impact on health, especially in Western-society. While inflammation is beneficial for the removal of microbes, low-grade inflammation never resolves and can cause or worsen other diseases. However, the process by which low-grade inflammation occurs is poorly understood. As lipopolysaccharide (LPS) is associated with chronic inflammatory diseases, we exposed murine bone-marrow derived monocytes to chronic LPS-stimulation at Low-dose (100pg/mL) or High-dose (1 µg/mL), as well as a PBS control. The cells were profiled for H3K27ac expression and gene expression. The gene expression of TRAM-deficient and IRAK-M-deficient mice with LPS exposure was also analyzed for mechanistic insight. We determined that many of the differences between the Low-dose and High-dose conditions are related to the TRIF-dependent pathway of TLR4 signaling. Furthermore, these changes are also seen in the epigenome, suggesting the epigenome may be what leads to the differential response. These findings further characterize the different means utilized in low-grade conditions, and how it might lead to a damaging, non-resolving state. Moreover, our data provide potential targets for future mechanistic or therapeutic studies.

ORGANISM(S): Mus musculus

PROVIDER: GSE168190 | GEO | 2021/03/18

REPOSITORIES: GEO

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