Abstract
Persistent activation of nuclear factor B (NF-κB) is very important in the modulation of macrophages cellular response to microbial infections. The deubiquitinase USP14, which is critical for ubiquitin-mediated proteasomal degradation of proteins, is known to be involved in cancer, neurological diseases, and aging. However, the mechanism by which USP14 regulates inflammation remains unclear. Here, we demonstrated that decreasing the deubiquitinase activity of USP14 resulted in reduced lipopolysaccharides (LPS)-mediated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 release in THP-1 and RAW264.7 cells. Meanwhile, USP14 knockdown by siRNA showed the same effects, with no cytotoxicity in THP-1 cells. Moreover, inhibiting the deubiquitinase activity of USP14 or USP14 knockdown resulted in decreased ERK1/2 and IκBα phosphorylation, increased amounts of the NF-κB inhibitor IκBα, and reduced NF-κB p65 transport from the cytoplasm into nucleus. These findings suggested that USP14 induces NF-κB activity and ERK1/2 phosphorylation triggered by microbial infection.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81400231), Pearl River S&T Nova Program of Guangzhou (No. 201506010071) General Project (1201420465) from Guangzhou Education Commission, the Science and Technology Planning Project of Guangdong Province, China (2014A020221059), Guangzhou Medical and health science and technology project (20141A011079).
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Ningning Liu, Tianyu Kong and Xiaohua Chen contributed equally to this work.
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Liu, N., Kong, T., Chen, X. et al. Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation. Mol Cell Biochem 431, 87–96 (2017). https://doi.org/10.1007/s11010-017-2978-0
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DOI: https://doi.org/10.1007/s11010-017-2978-0