USP25 promotes endotoxin tolerance via suppressing K48-linked ubiquitination and degradation of TRAF3 in Kupffer cells

Wen, Jian; He, Bo; Chen, Nan; Zhang, Wenfeng; Zhu, Xiaoyan; Li, Peizhi; Gong, Jianping

doi:10.1016/j.molimm.2018.12.017

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…There are recent studies that have shown that IL17 modulates macrophage phenotype in a NF-κB–dependent manner after 48 hours of exposure. 49 Other studies, using a similar condition media experimental design, have shown that inflammatory factors may be induced by IL17 in macrophages after 24 hours. 50 Second, inflammatory factor induced by IL17, which may be independent of USP25, also may involve noncanonical factors such as glycogen synthase kinase 3 and CCAAT enhancer binding protein alpha.…”

Section: Discussionmentioning

confidence: 95%

USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

Liu

Luo

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 95%

USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

Liu

Luo

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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“…However, the present study did not evaluate the direct interaction between USP25 and TRAF3. Several studies have reported the mechanisms underlying USP25-TRAF3 interactions (26,27,47). Notably, USP25 has been reported to specifically remove the K48-linked ubiquitin chain from TRAF3, which increases cellular abundance of TRAF3 and balances production of type I IFNs and inflammatory cytokines following TLR4 activation (26).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium

Chang

Tan

et al. 2022

Mol Med Rep

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Ubiquitin-specific peptidase 25 (USP25) is a key deubiquitylase belonging to the USP superfamily that is primarily involved in inflammation and the immune response. Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that is regarded as the master switch that initiates and maintains the type 2 immune response in allergic rhinitis (AR). However, the molecular mechanisms by which USP25 regulates TSLP signaling in the nasal epithelium in AR remain unclear. The present study assessed the protein expression levels of USP25 in the nasal epithelium of patients with AR. Moreover, USP25 knockout (KO) and wild-type (WT) mice were treated with ovalbumin (OVA) to establish a model of AR. The results of western blotting and immunohistochemistry in the present study demonstrated that the protein expression levels of USP25 were significantly decreased in the nasal mucosa of patients with AR and AR mice, whereas the protein expression levels of TSLP were significantly increased. Allergic inflammation was more severe in USP25 KO mice compared with WT mice exposed to OVA, as demonstrated by increased nose scratching and sneezing, increased eosinophil infiltration, goblet cell hyperplasia and enhanced T helper type 2 (Th2) cytokine production. The results of in vitro experiments demonstrated that silencing or overexpression of USP25 decreased or increased TNF receptor-associated factor 3 (TRAF3) protein expression levels, respectively, in human nasal epithelial cells, whereas TSLP protein expression levels were negatively associated with the expression of USP25 and TRAF3. In summary, USP25 downregulation enhanced TSLP signaling in the nasal mucosal epithelium via decreased TRAF3 expression, thereby exacerbating inflammation in AR. Therefore, USP25 may act as a novel therapeutic target in AR.

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“…TraF3 is expressed by numerous types of cell, including immune cells such as macrophages, B lymphocytes and T lymphocytes, and serves important roles in regulating the immune system (25). TraF3 functions mainly via ubiquitination (ub), including K48-linked ub and K63-linked ub (26). K48 polyubiquitination of TraF3 induces TraF3 degradation, which limits retinoic acid-inducible gene 1-induced type i interferon production in immune cells (24).…”

Section: Discussionmentioning

confidence: 99%

SMAC mimetic birinapant inhibits hepatocellular carcinoma growth by activating the cIAP1/TRAF3 signaling pathway

et al. 2020

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The present study investigated the effects and molecular mechanism of the second mitochondria-derived activator of caspase (SMac) mimetic birinapant on the proliferation and apoptotic rate of liver cancer cells. Western blotting and reverse transcription-quantitative Pcr were used to detect the protein and mrna expression levels of cellular inhibitor of apoptosis 1 (ciaP1) and tumor necrosis factor receptor-associated factor 3 (TraF3) in the liver cancer cell lines Huh7, H22 and HepG2, and the hepatocyte line aMl12. annexin V-FiTc and Transwell assays were used to assess the effect of birinapant pretreatment on the apoptotic rate and invasive ability of liver cancer cells. lentivirus-mediated silencing of TraF3 was performed in liver cancer cells. Western blotting was used to detect the lentivirus silencing efficiency. A subcutaneous hepatocellular carcinoma model was established in nude mice and 15 days after tumor induction the subcutaneous tumors were measured in each group. immunohistochemistry assays were used to detect the protein expression levels of proliferating cell nuclear antigen and caspase-3. The results suggested that the expression levels of ciaP1 and TraF3 were lower in Huh7, H22 and HepG2 cells compared with aMl12 cells. Pretreatment with birinapant promoted apoptosis and inhibited invasion of liver cancer cells by activating the ciaP1/TraF3 axis. Birinapant also promoted apoptosis and inhibited the growth of subcutaneous hepatocellular carcinoma tumors in nude mice. The present results suggested that the SMac mimetic birinapant may promote apoptosis, and inhibit the proliferation and invasion of liver cancer cells. The molecular mechanism responsible for the effects of birinapant may be related to activation of the ciaP1/TraF3 signaling pathway by birinapant in liver cancer cells.

show abstract

USP25 promotes endotoxin tolerance via suppressing K48-linked ubiquitination and degradation of TRAF3 in Kupffer cells

Cited by 16 publications

References 32 publications

USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium

SMAC mimetic birinapant inhibits hepatocellular carcinoma growth by activating the cIAP1/TRAF3 signaling pathway

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