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https://www.readbyqxmd.com/read/29296923/the-oncogenic-membrane-protein-lmp1-sequesters-traf3-in-b-cell-lymphoma-cells-to-produce-functional-traf3-deficiency
#1
Pradeep Bangalore-Prakash, Laura L Stunz, Nurbek Mambetsariev, Amy L Whillock, Bruce S Hostager, Gail A Bishop
Loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (TRAF3) are commonly found in human B-cell malignancies, especially multiple myeloma and B-cell lymphoma (BCL). B-cell TRAF3 deficiency results in enhanced cell survival, elevated activation receptor signaling, and increased activity of certain transcriptional pathways regulating expression of prosurvival proteins. A recent analysis of TRAF3 protein staining of ∼300 human BCL tissue samples revealed that a higher proportion of samples expressing the oncogenic Epstein-Barr virus-encoded protein latent membrane protein 1 (LMP1) showed low/negative TRAF3 staining than predicted...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285249/retinol-dehydrogenase-10-promotes-development-and-progression-of-human-glioma-via-the-tweak-nf-%C3%AE%C2%BAb-axis
#2
Feng Guan, Liang Wang, Shuyu Hao, Zhen Wu, Jian Bai, Zhuang Kang, Quan Zhou, Hong Chang, Hui Yin, Da Li, Kaibin Tian, Junpeng Ma, Guijun Zhang, Junting Zhang
Retinol dehydrogenase-10 (RDH10) is a member of the short-chain dehydrogenase/reductase family, which plays an important role in retinoic acid (RA) synthesis. Here, we show that RDH10 is highly expressed in human gliomas, and its expression correlates with tumor grade and patient survival times. In vitro, lentivirus-mediated shRNA knockdown of RDH10 suppressed glioma cell proliferation, survival, and invasiveness and cell cycle progression. In vivo, RDH10 knockdown reduced glioma growth in nude mice. Microarray analysis revealed that RDH10 silencing reduces expression of TNFRSF12A (Fn14), TNFSF12 (TWEAK), TRAF3, IKBKB (IKK-β), and BMPR2, while it increases expression of TRAF1, NFKBIA (IκBα), NFKBIE (IκBε), and TNFAIP3...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29278208/identification-of-the-multifaceted-chemopreventive-activity-of-curcumin-against-the-carcinogenic-potential-of-the-food-additive-kbro3
#3
Ismael Obaidi, Michael Higgins, Bojlul Bahar, Jessica L Davis, Tara McMorrow
BACKGROUND: Potassium bromate (KBrO3), a food additive, has been used in many bakery products as an oxidizing agent. It has been shown to induce renal cancer in many in-vitro and in-vivo experimental models Objectives: This study evaluated the carcinogenic potential of potassium bromate (KBrO3) and the chemopreventive mechanisms of the anti-oxidant and anti-inflammatory phytochemical, curcumin against KBrO3-induced carcinogenicity Method: Lactate dehydrogenase (LDH) cytotoxicity assay and morphological characteristics were used to assess curcumin's cytoprotective potential against KBrO3 toxicity...
December 26, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29233916/aging-impairs-both-primary-and-secondary-rig-i-signaling-for-interferon-induction-in-human-monocytes
#4
Ryan D Molony, Jenny T Nguyen, Yong Kong, Ruth R Montgomery, Albert C Shaw, Akiko Iwasaki
Adults older than 65 account for most of the deaths caused by respiratory influenza A virus (IAV) infections, but the underlying mechanisms for this susceptibility are poorly understood. IAV RNA is detected by the cytosolic sensor retinoic acid-inducible gene I (RIG-I), which induces the production of type I interferons (IFNs) that curtail the spread of the virus and promote the elimination of infected cells. We have previously identified a marked defect in the IAV-inducible secretion of type I IFNs, but not proinflammatory cytokines, in monocytes from older (>65 years) healthy human donors...
December 12, 2017: Science Signaling
https://www.readbyqxmd.com/read/29221114/interferon-%C3%AF-increases-bola-i-for-implantation-during-early-pregnancy-in-dairy-cows
#5
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...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215030/traf3-negatively-regulates-platelet-activation-and-thrombosis
#6
Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li
CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29196212/axl-activation-attenuates-neuroinflammation-by-inhibiting-the-tlr-traf-nf-%C3%AE%C2%BAb-pathway-after-mcao-in-rats
#7
Guangyong Wu, Devin W McBride, John H Zhang
BACKGROUND AND PURPOSE: Ischemic stroke activates Toll-like receptors (TLRs), triggering rapid inflammatory cytokine production. Axl signaling has multiple roles, including regulating cytokine secretion, clearing apoptotic cells, and maintaining cell survival, however, its role in inflammation after ischemic stroke has not been examined. We hypothesized that activation of Axl by recombinant Growth-arrest-specific protein 6 (rGas6) attenuates neuroinflammation by inhibiting the TLR/TRAF/NF-κB pathway after middle cerebral artery occlusion (MCAO) in rats...
November 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29177921/inhibitory-effects-and-related-molecular-mechanisms-of-total-flavonoids-in-mosla-chinensis-maxim-against-h1n1-influenza-virus
#8
Xiao-Xia Zhang, Qiao-Feng Wu, Yun-Liang Yan, Feng-Ling Zhang
OBJECTIVE: The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. METHODS: The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF...
November 24, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29150602/tlr7-mediated-viral-recognition-results-in-focal-type-i-interferon-secretion-by-dendritic-cells
#9
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146913/autophagy-acts-through-traf3-and-relb-to-regulate-gene-expression-via-antagonism-of-smad-proteins
#10
Alice C Newman, Alain J Kemp, Yvette Drabsch, Christian Behrends, Simon Wilkinson
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29028369/toll-like-receptors-significance-ligands-signaling-pathways-and-functions-in-mammals
#11
Mallenahally Kusha Vidya, V Girish Kumar, Veerasamy Sejian, Madiajagan Bagath, Govindan Krishnan, Raghavendra Bhatta
This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity...
October 13, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/29017949/tumor-necrosis-factor-receptor-associated-factor-3-from-anodonta-woodiana-is-an-important-factor-in-bivalve-immune-response-to-pathogen-infection
#12
Fufa Qu, Zhiming Xiang, Yingli Zhou, Yanping Qin, Ziniu Yu
Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional adaptor protein in innate and acquired immune system that plays a key role in the regulation of the RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling pathway in mammals. However, the immune function of TRAF3 homologs in freshwater mollusks is not well understood. In this study, we identified a bivalve TRAF3 gene (AwTRAF3) from Anodonta woodiana and investigated its potential roles during immune challenges. The present AwTRAF3 encoded a polypeptide of 562 amino acids with predicted molecular mass of 64...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28988112/caerulin-induced-pro-inflammatory-response-in-macrophages-requires-traf3-p38-signaling-activation
#13
Rongrong Jia, Jiali Ma, Shihao Xiang, Wenying Meng, Na Wang
Acute pancreatitis is a common threat to human health. Caerulin provokes severe inflammations, causing injuries to surrounding pancreatic cells. TNF receptor-associated factor 3 (TRAF3) is a highly versatile regulator of immune response. The current study aims to understand the potential effect of TRAF3 on caerulin-induced pro-inflammatory responses. In the primary-cultured mouse bone marrow-derived macrophages (BMDMs), caerulin induced TRAF3 protein stabilization, which formed a complex with mitogen-activated protein kinase kinase 3 (MKK3) to mediate downstream p38 activation...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28983055/pattern-of-somatic-mutations-in-patients-with-waldenstr%C3%A3-m-macroglobulinemia-or-igm-monoclonal-gammopathy-of-undetermined-significance
#14
Marzia Varettoni, Silvia Zibellini, Irene Defrancesco, Virginia Valeria Ferretti, Ettore Rizzo, Luca Malcovati, Anna Gallì, Matteo Giovanni Della Porta, Emanuela Boveri, Luca Arcaini, Chiara Candido, Marco Paulli, Mario Cazzola
We analyzed MYD88 and CXCR4 mutation status of 260 patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance using allele-specific real time quantitative PCR and Sanger sequencing respectively. A subgroup of 119 patients was further studied with next-generation sequencing of 11 target genes (MYD88, CXCR4, ARID1-A, KMT2D, NOTCH2, TP53, PRDM1, CD79B, TRAF3, MYBBP1A, TNFAIP3). MYD88 (L265P) was found at diagnosis in 91% of patients with Waldenström macroglobulinemia and in 60% of patients with IgM monoclonal gammopathy of undetermined significance using allele-specific PCR...
October 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28981114/essential-role-of-hcmv-deubiquitinase-in-promoting-oncogenesis-by-targeting-anti-viral-innate-immune-signaling-pathways
#15
Puja Kumari, Irene Saha, Athira Narayanan, Sathish Narayanan, Akinori Takaoka, Nachimuthu Senthil Kumar, Prafullakumar Tailor, Himanshu Kumar
Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown. Here, we identified a conserved herpesviral tegument protein known as pUL48 of HCMV, encoding deubiquitinase enzyme, as having a key role in carcinogenesis. We show using deubiquitinase sufficient- and deficient-HCMV that HCMV deubiquitinase is a key in inducing enhanced cellular metabolic activity through upregulation of several anti-apoptotic genes and downregulation of several pro-apoptotic genes expression...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28977602/dipeptidyl-peptidase-4-inhibition-with-saxagliptin-ameliorates-angiotensin-ii-induced-cardiac-diastolic-dysfunction-in-male-mice
#16
Scott M Brown, Cassandra E Smith, Alex I Meuth, Maloree Khan, Annayya R Aroor, Hannah M Cleeton, Gerald A Meininger, James R Sowers, Vincent G DeMarco, Bysani Chandrasekar, Ravi Nistala, Shawn B Bender
Activation of the renin-angiotensin-aldosterone system is common in hypertension and obesity and contributes to cardiac diastolic dysfunction, a condition for which no treatment currently exists. In light of recent reports that antihyperglycemia incretin enhancing dipeptidyl peptidase (DPP)-4 inhibitors exert cardioprotective effects, we examined the hypothesis that DPP-4 inhibition with saxagliptin (Saxa) attenuates angiotensin II (Ang II)-induced cardiac diastolic dysfunction. Male C57BL/6J mice were infused with either Ang II (500 ng/kg/min) or vehicle for 3 weeks receiving either Saxa (10 mg/kg/d) or placebo during the final 2 weeks...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28971844/traf3ip2-mediates-high-glucose-induced-endothelin-1-production-as-well-as-endothelin-1-induced-inflammation-in-endothelial-cells
#17
Jaume Padilla, Andrea Carpenter, Nitin Das Das, Hemanth K Kandikattu, Susana Lopez-Ongil, Luis A Martinez-Lemus, Ulrich Siebenlist, Vincent G DeMarco, Bysani Chandrasekar
Hyperglycemia-induced production of endothelin-1 (ET-1) is a hallmark of endothelial dysfunction in diabetes. While the detrimental vascular effects of increased ET-1 are well-known, the molecular mechanisms regulating endothelial synthesis of ET-1 in the setting of diabetes remain largely unidentified. Here we show that adapter molecule TRAF3 Interacting Protein 2 (TRAF3IP2) mediates high glucose-induced ET-1 production in endothelial cells and ET-1-mediated endothelial cell inflammation. Specifically, we found that high glucose upregulated TRAF3IP2 in human aortic endothelial cells, which subsequently led to activation of c-Jun N-terminal kinase (JNK) and IκB kinase beta (IKKβ)...
September 29, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28951223/identification-and-characterization-of-cd40-from-humphead-snapper-lutjanus-sanguineus
#18
Jia Cai, Yunxia Fan, Hongli Xia, Yishan Lu, Jichang Jian, Zaohe Wu
CD40 is known as "master switch" in immune response to pathogen infection in mammals. However, limited information of CD40 is known in lower vertebrates. In this study, a novel CD40 homolog (Ls-CD40) was cloned and characterized from humphead snapper, Lutjanus sanguineus. The Ls-CD40 cDNA composed of 2073 bp with a 69 bp of 5'-UTR, a 1020 bp of 3'-UTR and an open reading frame (ORF) of 984 bp, encoding 327 amino acid residues. Sequence analysis showed that Ls-CD40 contained a single peptide, a transmembrane domain and four cysteine-rich domains...
September 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28846086/the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#19
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...
October 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
#20
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 have revolutionized therapy in chronic lymphocytic leukemia (CLL), responses are incomplete. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B cells resident in the protective lymphoid niches. B-cell activating factor (BAFF) is critical to the survival of both healthy and neoplastic B cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized...
November 2017: Haematologica
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