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https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#1
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
DEAD-box (DDX) helicases are vital for the recognition of RNA and metabolism and are critical for the initiation of antiviral innate immunity. Modification of RNA is involved in many biological processes; however, its role in antiviral innate immunity has remained unclear. Here we found that nuclear DDX member DDX46 inhibited the production of type I interferons after viral infection. DDX46 bound Mavs, Traf3 and Traf6 transcripts (which encode signaling molecules involved in antiviral responses) via their conserved CCGGUU element...
August 28, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28838991/syk-inhibition-thwarts-the-baff-b-cell-receptor-crosstalk-and-thereby-antagonizes-mcl-1-in-chronic-lymphocytic-leukemia
#2
Cody Paiva, Taylor A Rowland, Bhargava Sreekantham, Claire Godbersen, Scott R Best, Prabhjot Kaur, Marc M Loriaux, Stephen E F Spurgeon, Olga V Danilova, Alexey V Danilov
Although small molecule inhibitors of B-cell receptor-associated kinases revolutionized therapy in chronic lymphocytic leukemia, they provide for incomplete responses. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B-cells resident in the protective lymphoid niches. BAFF is critical in survival of both healthy and neoplastic B-cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized. Here we show that BAFF elicited resistance to spontaneous and drug-induced apoptosis in stromal co-cultures, induced activation of both canonical and non-canonical NFκB signaling pathways and triggered B-cell receptor signaling in chronic lymphocytic leukemia cells, independent of IGHV mutational status...
August 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28753533/role-of-traf3-in-neurological-and-cardiovascular-diseases-an-overview-of-recent-studies
#3
Natalia Cullell, Elena Muiño, Caty Carrera, Nuria Torres, Jerzy Krupinski, Israel Fernandez-Cadenas
Tumour necrosis factor receptor-associated factor 3 (TRAF3) is a member of the TRAF adaptor protein family, which exerts different effects on the cell depending on the receptor to which it binds and the cell type in which it is expressed. TRAF3 is a major regulator of the innate immune response. To perform its functions properly, TRAF3 is transcriptionally and epigenetically regulated. At the transcriptional level, TRAF3 expression has been associated with neurological and cardiovascular diseases including stroke, among other pathologies...
September 26, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28751620/interferon-%C3%AF-increases-bola-i-for-implantation-during-early-pregnancy-in-dairy-cows
#4
Zhe Zhu, Binbin Li, Yue Wu, Xiao Wang, GanZhen Deng
Interferon-τ (IFN-τ) signals pregnancy recognition in ruminants. We investigated the effects of IFN-τ produced by embryo trophoblastic cells (ETCs) on expression of bovine leukocyte antigen-I (BoLA-I), a bovine analogue of human MHC-I, in endometrial luminal epithelial cells (EECs) during early pregnancy in dairy cows. Expression of IFN-τ and BoLA-I was increased in endometrial tissues during early pregnancy. Expression of the anti-inflammatory cytokine IL-10 was increased in endometrial tissues, while expression of the pro-inflammatory cytokine IL-6 was decreased, indicating immunosuppression...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28750349/escherichia-coli-maltose-binding-protein-mbp-activates-mouse-th1-through-tlr2-mediated-myd88-dependent-pathway-and-tlr4-mediated-trif-dependent-pathway
#5
GuoMu Liu, YiXin Zhang, NanNan Zhang, WeiHua Ni, Jing Jie, LiNa Jiang, GuiXiang Tai
MBP (maltose-binding protein) is a component of Escherichia coli. Our previous study found that MBP directly induces the activation of Th1 (T helper type 1), but the molecular mechanism remains unclear. In the present study, CD4(+)T cells were purified from the spleens of normal mice using antibody-coated immunomagnetic beads by negative selection. CD4(+)T cells activated with a CD3/CD28 antibody were stimulated with MBP. The results indicated that MBP elevated IFN-γ mRNA levels in activated CD4(+)T cells and promoted IFN-γ production from activated CD4(+)T cells...
July 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28745813/subversion-of-innate-immune-responses-by-francisella-involves-the-disruption-of-traf3-and-traf6-signaling-complexes
#6
Daniela Putzova, Swarupa Panda, Anetta Härtlova, Jiří Stulík, Nelson O Gekara
The success of pathogens depends on their ability to circumvent immune defenses. Francisella tularensis is one of the most infectious bacteria known. The remarkable virulence of Francisella is believed to be due to its capacity to evade or subvert the immune system, but how remains obscure. Here we show that Francisella triggers but concomitantly inhibits the Toll-like receptor (TLR), RIG-I-like receptor (RLR) and Cytoplasmic DNA (CDR) pathways. Francisella subverts these pathways at least in part by inhibiting K63-linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of PRRs...
July 26, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28717359/the-c-terminal-effector-domain-of-non-structural-protein-1-of-influenza-a-virus-blocks-ifn-%C3%AE-production-by-targeting-tnf-receptor-associated-factor-3
#7
Wei Qian, Xiaoqin Wei, Kelei Guo, Yongtao Li, Xian Lin, Zhong Zou, Hongbo Zhou, Meilin Jin
Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28682481/significant-association-between-tnfaip3-inactivation-and-biased-immunoglobulin-heavy-chain-variable-region-4-34-usage-in-mucosa-associated-lymphoid-tissue-lymphoma
#8
Sarah Moody, Leire Escudero-Ibarz, Ming Wang, Alexandra Clipson, Eguzkine Ochoa Ruiz, Deborah Dunn-Walters, Xuemin Xue, Naiyan Zeng, Alistair Robson, Shih-Sung Chuang, Sergio Cogliatti, Hongxiang Liu, John Goodlad, Margaret Ashton-Key, Markus Raderer, Yingwen Bi, Ming-Qing Du
Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites...
September 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28627449/microrna-214-regulates-immunity-related-genes-in-bovine-mammary-epithelial-cells-by-targeting-nfatc3-and-traf3
#9
Ning Song, Xingping Wang, Linsheng Gui, Sayed Haidar Abbas Raza, Zhuoma Luoreng, Linsen Zan
In human, microRNA-214 (miR-214) plays crucial roles in mechanisms of immunity. However, the potential importance of miR-214 in immune mechanisms in dairy cows has not been investigated. In this study, we assessed potential immunity-related functions of miR-214 in human 293A cells and in bovine mammary epithelial cells (BMECs). We found that NFATc3 and TRAF3 could be targeted by miR-214 in both 293A cells and BMECs. We also found that miR-214 indirectly inhibited the expression of MAP3K14, TBK1 and inflammatory cytokines IL-6 and IL-1β...
June 13, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28559278/the-p90-ribosomal-s6-kinase-ubr5-pathway-controls-toll-like-receptor-signaling-via-mirna-induced-translational-inhibition-of-tumor-necrosis-factor-receptor-associated-factor-3
#10
Jin Hwa Cho, Sung Ah Kim, Yeon-Soo Seo, Sung Goo Park, Byoung Chul Park, Jeong-Hoon Kim, Sunhong Kim
MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression. For example, miRNAs repress gene expression by recruiting the miRNA-induced silencing complex (miRISC), a ribonucleoprotein complex that contains miRNA-engaged Argonaute (Ago) and the scaffold protein GW182. Recently, ubiquitin-protein ligase E3 component N-recognin 5 (UBR5) has been identified as a component of miRISC. UBR5 directly interacts with GW182 proteins and participates in miRNA silencing by recruiting downstream effectors, such as the translation regulator DEAD-box helicase 6 (DDX6) and transducer of ERBB2,1/2,2 (Tob1/2), to the Ago-GW182 complex...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#11
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28499194/quercetin-ameliorates-imiquimod-induced-psoriasis-like-skin-inflammation-in-mice-via-the-nf-%C3%AE%C2%BAb-pathway
#12
Haiming Chen, Chuanjian Lu, Huazhen Liu, Maojie Wang, Hui Zhao, Yuhong Yan, Ling Han
Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action...
May 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28479387/the-effects-of-tlr3-trif-and-traf3-snps-and-interactions-with-environmental-factors-on-type-2-diabetes-mellitus-and-vascular-complications-in-a-han-chinese-population
#13
Zixing Zhou, Chengli Zeng, Lihong Nie, Shiqi Huang, Congcong Guo, Di Xiao, Yajing Han, Xiaohong Ye, Meiling Ou, Chuican Huang, Xingguang Ye, Zihao Wen, Guang Yang, Chunxia Jing
Toll-like receptor 3 (TLR3) is involved in type I interferon-β (IFN-β) via TIR-domain-containing adapter-inducing interferon-β (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated...
August 30, 2017: Gene
https://www.readbyqxmd.com/read/28438834/rankl-cytokine-enhances-tnf-induced-osteoclastogenesis-independently-of-tnf-receptor-associated-factor-traf-6-by-degrading-traf3-in-osteoclast-precursors
#14
Zhenqiang Yao, Wei Lei, Rong Duan, Yanyun Li, Lu Luo, Brendan F Boyce
Cytokines, including receptor activator of nuclear factor κB ligand (RANKL) and TNF, induce increased osteoclast (OC) formation and bone loss in postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can independently induce OC formation in vitro from WT OC precursors via TNF receptor-associated factor (TRAF) adaptor proteins, which bind to their receptors. Of these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro However, the molecular mechanisms involved remain incompletely understood...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28418082/non-digestible-carbohydrates-supplementation-increases-mir-32-expression-in-the-healthy-human-colorectal-epithelium-a-randomized-controlled-trial
#15
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Bart Lagerwaard, Seamus Kelly, D Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS, and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomized, double-blind, placebo-controlled dietary intervention...
September 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28391724/usp19-suppresses-cellular-type-i-interferon-signaling-by-targeting-traf3-for-deubiquitination
#16
Zhiwen Gu, Weifeng Shi, Li Zhang, Zhilin Hu, Chao Xu
AIM: To investigate host factors that mediate the immune escape of enterovirus 71 (EV71) in the context of deubiquitinating enzymes. MATERIALS & METHODS: Utilize PCR array to screen candidate genes that may be involved in EV71-induced cellular antiviral immune responses, and utilize protein mass spectrometry analysis to identify the functional targets of the candidate regulator. RESULTS: EV71 infection induces the upregulation of ubiquitin-specific protease 19 (USP19) gene expression, which negatively regulates cellular antiviral type I interferon signaling...
April 10, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28377715/protective-effects-of-dioscin-against-lipopolysaccharide-induced-acute-lung-injury-through-inhibition-of-oxidative-stress-and-inflammation
#17
Hong Yao, Yiping Sun, Shasha Song, Yan Qi, Xufeng Tao, Lina Xu, Lianhong Yin, Xu Han, Youwei Xu, Hua Li, Huijun Sun, Jinyong Peng
The protective effects of dioscin, a natural steroidal saponin from some medicinal plants including Dioscorea nipponica Makino, against lipopolysaccharide (LPS)- induced acute liver and renal damages have been reported in our previous works. However, the actions of dioscin against LPS-induced acute lung injury (ALI) is still unknown. In the present study, we investigated the effects and mechanisms of dioscin against LPS-induced ALI in vitro and in vivo. The results showed that dioscin obviously inhibited cell proliferation and markedly decreased reactive oxidative species level in 16HBE cells treated by LPS...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28295222/traf3-cyld-mutations-identify-a-distinct-subset-of-human-papillomavirus-associated-head-and-neck-squamous-cell-carcinoma
#18
Michael Hajek, Andrew Sewell, Susan Kaech, Barbara Burtness, Wendell G Yarbrough, Natalia Issaeva
BACKGROUND: The incidence of human papillomavirus (HPV)-associated (HPV-positive) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and continues to rise. Newly diagnosed HPV-positive HNSCCs in the United States currently outnumber any other HPV-associated cancers, including cervical cancer. Despite introduction of the HPV vaccine, the epidemic of HPV-positive HNSCC is expected to continue for approximately 60 years. Compared with patients who have tobacco-associated HNSCC, those who have HPV-positive HNSCC have better overall survival and response to treatment...
May 15, 2017: Cancer
https://www.readbyqxmd.com/read/28295216/genetic-alterations-in-traf3-and-cyld-that-regulate-nuclear-factor-%C3%AE%C2%BAb-and-interferon-signaling-define-head-and-neck-cancer-subsets-harboring-human-papillomavirus
#19
Tony Chen, Jialing Zhang, Zhong Chen, Carter Van Waes
No abstract text is available yet for this article.
May 15, 2017: Cancer
https://www.readbyqxmd.com/read/28286228/the-smac-mimetic-birinapant-attenuates-lipopolysaccharide-induced-liver-injury-by-inhibiting-the-tumor-necrosis-factor-receptor-associated-factor-3-degradation-in-kupffer-cells
#20
Hongxiang Liu, Rui Liao, Kun He, Xiwen Zhu, Peizhi Li, Jianping Gong
It was demonstrated that second mitochondria-derived activator of caspases (SMAC) mimetic inhibites tumor necrosis factor receptor-associated factor 3 (TRAF3) degradation and the mitogen-activated protein kinase (MAPK) signaling pathway activation induced by lipopolysaccharide (LPS) in vitro. However, the effect of Smac mimetic in vivo is not clear. The present study was to investigate the role of Smac mimetic in LPS-induced liver injury in mice and its possible mechanism. An animal model of LPS-induced liver injury was established by intraperitoneally injecting mice with 10mg/kg LPS pretreatment with or without Smac mimetic birinapant (30mg/kg body weight)...
March 9, 2017: Immunology Letters
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