title: Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation.
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.
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Kong
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Hongjiao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Emergency, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China. xiongxuming9@126.com.
authors.forename: Xuming
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Critical Care Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, Guangdong, People's Republic of China. zhzhhicu@126.com.
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D000067996:RAW 264.7 Cells; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C498143:RELA protein, human; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C509299:USP14 protein, human; C469268:Usp14 protein, mouse; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D043222:Ubiquitin Thiolesterase
keywords: Deubiquitinase; ERK; Inflammation; NF-κB; USP14