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https://www.readbyqxmd.com/read/28549054/regulation-of-mir-146a-and-traf6-in-the-diagnose-of-lupus-nephritis
#1
Yunfeng Zhu, Zhenzhen Xue, Lizhe Di
BACKGROUND Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). This study tested miR-146a and its target gene TRAF6 expression in LN patients and discussed their relationship with LN. MATERIAL AND METHODS One hundred twenty-eight LN patients and 30 healthy controls were enrolled in this study. MiR-146a and TRAF6 expression in peripheral blood mononuclear cells (PBMCs) were detected. Serum cytokines content was determined by ELISA. The diagnostic role of miR-146a and TRAF6 in LN activity was evaluated by ROC curve...
May 26, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28547582/ran-binding-protein-9-ranbpm-binds-ifn-%C3%AE-r1-in-the-ifn-%C3%AE-signaling-pathway
#2
Junwen Zhang, Xiaojie Cong, Jiajie Zhaoqiao, Xia Yang, Meng Li, Hong Chen, Ruifang Mi, Guishan Jin, Fusheng Liu, Bing-Ren Huang
Like the type I interferons (IFNs), the recently discovered cytokine IFN-λ displays antiviral, antiproliferative, and proapoptotic activities, mediated by a heterodimeric IFN-λ receptor complex composed of a unique IFN-λR1 chain and the IL-10R2 chain. However, the molecular mechanism of the IFN-λ-regulated pathway remains unclear. In this study, we newly identified RAN-binding protein M (RanBPM) as a binding partner of IFN-λR1. The interaction between RanBPM and IFN-λR1 was identified with a glutathione S-transferase pull-down assay and coimmunoprecipitation experiments...
May 24, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28545737/microrna-146a-governs-fibroblast-activation-and-joint-pathology-in-arthritis
#3
Victoria Saferding, Antonia Puchner, Eliana Goncalves-Alves, Melanie Hofmann, Michael Bonelli, Julia S Brunner, Emine Sahin, Birgit Niederreiter, Silvia Hayer, Hans P Kiener, Elisa Einwallner, Ramzi Nehmar, Raphael Carapito, Philippe Georgel, Marije I Koenders, Mark Boldin, Gernot Schabbauer, Mariola Kurowska-Stolarska, Günter Steiner, Josef S Smolen, Kurt Redlich, Stephan Blüml
Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation...
May 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28543180/traf6-participates-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats-through-inhibiting-autophagy-and-promoting-oxidative-stress
#4
Yang Dou, Haitao Shen, Dongxia Feng, Haiying Li, Xiaodi Tian, Jian Zhang, Zhong Wang, Gang Chen
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a member of the TRAF family and an important multifunctional intracellular adaptin of the tumor necrosis factor (TNF) superfamily and toll/IL-1 receptor (TIR) superfamily. TRAF6 has been studied in several central nervous system (CNS) diseases, including ischemic stroke, traumatic brain injury and neurodegenerative diseases, but its role in subarachnoid hemorrhage (SAH) has not been fully illustrated. This study was designed to explore changes of expression level and potential roles and mechanisms of TRAF6 in early brain injury (EBI) after SAH by using a Sprague-Dawley rat model of SAH induced in 0...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28522566/nedd8-modification-of-cullin-5-regulates-lipopolysaccharide-induced-acute-lung-injury
#5
Ziyan Zhu, Lei Sun, Rui Hao, Hongchao Jiang, Feng Qian, Richard D Ye
Lung infections are major causes of acute lung injury (ALI), with limited effective treatment available. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential adaptor regulating Toll-like receptors (TLRs). We recently identified Cullin-5 (Cul-5) as a prominent component in the regulation of TRAF6 polyubiquitination, but its physiological significance in acute lung injury has not been explored. In this study, we investigated the potential role of Cul-5 in regulating ALI using mice receiving intratracheal instillation of LPS...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28513840/histomorphology-and-innate-immunity-during-the-progression-of-osteoarthritis-does-synovitis-affect-cartilage-degradation
#6
Huan Wang, Qingguo Wang, Meijuan Yang, Lili Yang, Weili Wang, Haobin Ding, Dong Zhang, Jing Xu, Xuezhang Tang, Haitao Ding, Qingfu Wang
Osteoarthritis (OA) is a common chronic degenerative disease that affects all joints. At present, the pathological processes and mechanisms of OA are still unclear. Innate immunity, a key player in damage to the structure of the joint and the mechanism by which the host attempts to repair OA, affects all pathological stages of the disease. In the present study, our aim was to assess changes in innate immunity during the pathological processes of OA in articular cartilage (AC) and the synovial membrane (SM), which are the major structures in joints, and to systematically examine the histological changes in AC and SM in mild, moderate and severe cases of OA, in order to further speculate about the manner in which the interactions of AC and SM are facilitated by innate immunity...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28507161/interleukin-1-and-traf6-dependent-activation-of-tak1-in-the-absence-of-tab2-and-tab3
#7
Jiazhen Zhang, Thomas Macartney, Mark Peggie, Philip Cohen
Interleukin-1 (IL-1) signaling induces the formation of Lys63-linked ubiquitin (K63-Ub) chains, which are thought to activate the "master" protein kinase TAK1 by interacting with its TAB2 and TAB3 subunits. Here, we report that IL-1b can also activate the TAB1-TAK1 heterodimer present in TAB2/TAB3 double knock-out (DKO) IL-1 receptor-expressing cells. The IL-1b-dependent activation of the TAB1-TAK1 heterodimer in TAB2/3 DKO cells required the expression and E3 ligase activity of TRAF6 and was reduced by the siRNA knock-down of Ubc13, an E2 conjugating enzyme that directs the formation of K63-Ub chains...
May 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28507064/tumor-necrosis-factor-receptor-associated-factor-6-traf6-mediates-ubiquitination-dependent-stat3-activation-upon-salmonella-typhimurium-infection
#8
Hai-Hua Ruan, Zhen Zhang, Su-Ying Wang, Logan M Nickels, Li Tian, Jian-Jun Qiao, Jun Zhu
Salmonella enterica serovar Typhimurium (S Typhimurium) can inject effector proteins into host cells via Type III secretion systems (T3SSs). These effector proteins modulate a variety of host transcriptional responses to facilitate bacterial growth and survival. Here, we show that S Typhimurium infection of host cells specifically induces ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). This TRAF6 ubiquitination is triggered by the Salmonella pathogenicity island-1 (SPI-I) T3SS effectors SopB and SopE2...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28506585/c21-steroidal-pregnane-sapogenins-and-their-derivatives-as-anti-inflammatory-agents
#9
Lie-Jun Huang, Shao-Ru Chen, Chun-Mao Yuan, Wei Gu, Bao-Jian Guo, Yi-Tao Wang, Ying Wang, Xiao-Jiang Hao
During the screening of natural anti-inflammatory agent, we identified some C21-steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4-initiatedinflammatory responses respectively. Treatment with active compounds 10, 2j and 3p failed to impact tumor necrosis factor-α (TNF-α) induced nucleus translocation of NF-κB p65 subunit. However, these compounds regulated distinct canonical or non-canonical NF-κB family members. Ectopic expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory activity of the compounds on production of pro-inflammatory cytokines downstream of TLR4...
May 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28506571/tumor-necrosis-factor-receptor-associated-factor-traf-6-inhibition-mitigates-the-pro-inflammatory-roles-and-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#10
Lang-Jing Zhu, Tie-Cheng Yang, Qiang Wu, Li-Ping Yuan, Zhen-Wei Chen, Min-Hong Luo, Hai-Ou Zeng, Dong-Ling He, Cai-Ju Mo
BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs...
May 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28494768/inhibition-of-cd40-traf6-interactions-by-the-small-molecule-inhibitor-6877002-reduces-neuroinflammation
#11
Suzanne A B M Aarts, Tom T P Seijkens, Pascal J H Kusters, Susanne M A van der Pol, Barbara Zarzycka, Priscilla D A M Heijnen, Linda Beckers, Myrthe den Toom, Marion J J Gijbels, Louis Boon, Christian Weber, Helga E de Vries, Gerry A F Nicolaes, Christine D Dijkstra, Gijs Kooij, Esther Lutgens
BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across the blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells to induce inflammation and leukocyte trafficking, we explored the hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate neuro-inflammation...
May 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28480979/down-regulation-of-trif-tlr3-and-mavs-in-hcv-infected-liver-correlates-with-the-outcome-of-infection
#12
Premashis Kar, Deepak Kumar, Phani Kumar Gumma, Soumya Jyoti Chowdhury, Vijay Kumar Karra
AIMS: In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-β (TRIF) and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF and TRAF6 outcome of HCV infection...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28475177/the-role-of-hybrid-ubiquitin-chains-in-the-myd88-and-other-innate-immune-signalling-pathways
#13
REVIEW
Philip Cohen, Sam Strickson
The adaptor protein MyD88 is required for signal transmission by toll-like receptors and receptors of the interleukin-1 family of cytokines. MyD88 signalling triggers the formation of Lys63-linked and Met1-linked ubiquitin (K63-Ub, M1-Ub) chains within minutes. The K63-Ub chains, which are formed by the E3 ubiquitin ligases TRAF6, Pellino1 and Pellino2, activate TAK1, the master kinase that switches on mitogen-activated protein (MAP) kinase cascades and initiates activation of the canonical IκB kinase (IKK) complex...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28470929/down-regulation-of-increased-traf6-expression-in-the-peripheral-mononuclear-cells-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-by-an-ebv-eber1-specific-synthetic-single-stranded-complementary-dna-molecule
#14
Sándor Sipka, Erika Zilahi, Gábor Papp, Ji-Qing Chen, Andrea Nagy, Katalin Hegyi, József Kónya, Margit Zeher
AIM: We described earlier a simultaneously increased that the increased expression of miRNA-146a/b was accompanied by an increase in the expression of and TRAF6 and a decrease in the expression of IRAK1 genes in the peripheral mononuclear cells (PBMCs) of patients with primary Sjogren's syndrome (pSS) patients. Recently, the expression of EBV encoded. RNA (EBER) was published in the B cells of salivary glands of in pSS. In the present study, we applied an EBV-EBER1 specific synthetic single stranded complementary DNA molecule (EBV-EBER1-cDNA) to test whether any EBER1 related effect exists also in PBMCs of pSS patients...
May 3, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28458348/diarylheptanoid-hirsutenone-attenuates-osteoclastogenesis-by-suppressing-ifn%C3%AE-and-nf-%C3%AE%C2%BAb-signaling-in-th1-and-preosteoclastic-cells
#15
Do Ik Lee, Su Kil Jang, Da Woon Park, Seung Tae Kim, Jun Sub Park, Bo Ram Jo, Jung Youl Park, Hee Yong Park, Seong Soo Joo
The aim of the present study was to examine the inhibitory roles and mechanisms of hirsutenone (HTN) in the regulation of osteoclastogenesis. Gene levels were compared to assure the effects of HTN on osteoclastogenesis in mouse splenocytes/CD4(+) T cells, mouse macrophage-like cell line RAW264.7 (preosteoclast), MG63 (osteoblast), and RPMI1788 (B cell) cells. The mechanism by which HTN regulates the degradation of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits inhibitor of kappaB (IκB) and nuclear factor-kappaB (NF-κB) signaling was examined by Western blotting and luciferase reporter assays...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28456576/influence-of-the-total-saponin-fraction-from-dioscorea-nipponica-makino-on-tlr2-4-il1r-receptor-singnal-pathway-in-rats-of-gouty-arthritis
#16
Qi Zhou, Fang Fang Lin, Shu Min Liu, Xiao Fang Sui
ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea nipponica Makino have been extensively used in traditional medicine for the treatment of arthritic diseases, particularly gouty arthritis (GA). MATERIALS AND METHODS: Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). The mRNA and protein expression levels of TLR2, TLR4, IRAK1, TRAF6, TAK1, IKKα, IκBα and NF-κB in the synovial tissue of joint were detected by realtime PCR and WB methods respetively...
April 26, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28449847/loss-of-wdfy3-ameliorates-severity-of-serum-transfer-induced-arthritis-independently-of-autophagy
#17
Dennis J Wu, Iannis E Adamopoulos
WDFY3 is a master regulator of selective autophagy that we recently showed to interact with TRAF6 and augment RANKL-induced osteoclastogenesis in vitro and in vivo via the NF-κB pathway. Since the NF-κB pathway plays a major role in inflammation herein, we investigate the role of WDFY3 in an arthritis animal model. Our data show that WDFY3 conditional knockout mice (Wdfy3(loxP/loxP)-LysM-Cre+) were protected in the K/BxN serum transfer-induced arthritis animal model. These effects were independent of alterations in starvation-induced autophagy as evidenced by Western blot analysis of the autophagy marker LC3, autophagosome formation in osteoclast precursors and lysosome formation in osteoclasts derived from WDFY3-cKO mice compared to controls...
April 22, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28440423/upregulated-microrna-429-inhibits-the-migration-of-hcc-cells-by-targeting-traf6-through-the-nf-%C3%AE%C2%BAb-pathway
#18
Peng Wang, Jia Cao, Shihai Liu, Huazheng Pan, Xiangping Liu, Aihua Sui, Liping Wang, Ruyong Yao, Zimin Liu, Jun Liang
Increasing evidence indicates that miR-429 is involved in tumor suppression in various human cancers. however, its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that miR-429 was significantly downregulated in HCC tissue samples and cell lines. Upregulation of miR-429 markedly suppressed proliferation and migration of HCC cells. Moreover, we identified TRAF6 as a direct target of miR-429. Downregulation of TRAF6 partially attenuated the oncogenic effect of anti‑miR-429 on HCC cells...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440395/microrna-mediated-inflammatory-responses-induced-by-cryptococcus-neoformans-are-dependent-on-the-nf-%C3%AE%C2%BAb-pathway-in-human-monocytes
#19
Hong Chen, Yi Jin, Huan Chen, Ningxin Liao, Yan Wang, Jianghan Chen
Cryptococcosis is a significant invasive fungal infection with noteworthy morbidity and mortality that is usually caused by either Cryptococcus neoformans (C. neoformans) or Cryptococcus gattii (C. gattii). Epidemiological studies have indicated that C. neoformans are more often reported in immunocompromised and immunocompetent patients. It has been well established that the cytokine profile of the host markedly affects the outcome of cryptococcal disease, and the negative regulators of microRNAs(miRs or miRNAs) are critically important for immunomodulation...
April 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28439546/inositol-polyphosphate-multikinase-promotes-toll-like-receptor-induced-inflammation-by-stabilizing-traf6
#20
Eunha Kim, Jiyoon Beon, Seulgi Lee, Seung Ju Park, Hyoungjoon Ahn, Min Gyu Kim, Jeong Eun Park, Wooseob Kim, Jae-Min Yuk, Suk-Jo Kang, Seung-Hyo Lee, Eun-Kyeong Jo, Rho Hyun Seong, Seyun Kim
Toll-like receptor (TLR) signaling is tightly controlled to protect hosts from microorganisms while simultaneously preventing uncontrolled immune responses. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a critical mediator of TLR signaling, but the precise mechanism of how TRAF6 protein stability is strictly controlled still remains obscure. We show that myeloid-specific deletion of inositol polyphosphate multikinase (IPMK), which has both inositol polyphosphate kinase activities and noncatalytic signaling functions, protects mice against polymicrobial sepsis and lipopolysaccharide-induced systemic inflammation...
April 2017: Science Advances
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