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bioRxiv · 10.1101/2021.03.28.437377

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

Naler, L. B.·Hsieh, Y.-P.·Geng, S.·Zhou, Z.·Li, L.·Lu, C.
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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. The process by which low-grade inflammation occurs remains poorly understood. Here we exposed murine bone-marrow derived monocytes to chronic lipopolysaccharide (LPS) stimulation at low dose or high dose, as well as a PBS control. The cells were profiled for genome-wide H3K27ac modification and gene expression. The gene expression of TRAM-deficient and IRAK-M-deficient monocytes with LPS exposure was also analyzed. We discover that low-grade inflammation preferentially utilizes the TRAM/TRIF-dependent pathway of TLR4 signaling, and induces the expression of interferon response genes. In contrast, acute inflammation uniquely upregulates metabolic and proliferative pathways that also appear to be TRAM-dependent. The extensive differences in the epigenomic landscape between low-dose and high-dose conditions suggest the importance of epigenetic regulations in driving differential responses. Our data provide potential targets for future mechanistic or therapeutic studies.

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Naler, L. B., Hsieh, Y.-P., Geng, S., Zhou, Z., Li, L., Lu, C.. 2021-03-29. Epigenomic and transcriptomic differences between low-grade and acute inflammation in LPS-induced murine immune cells. https://doi.org/10.1101/2021.03.28.437377

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