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https://www.readbyqxmd.com/read/28432355/basal-autophagy-prevents-autoactivation-or-enhancement-of-inflammatory-signals-by-targeting-monomeric-myd88
#1
Takeshi Into, Toshi Horie, Megumi Inomata, Jin Gohda, Jun-Ichiro Inoue, Yukitaka Murakami, Shumpei Niida
Autophagy, the processes of delivery of intracellular components to lysosomes, regulates induction of inflammation. Inducible macroautophagy degrades inflammasomes and dysfunctional mitochondria to downregulate inflammatory signals. Nonetheless, the effects of constitutive basal autophagy on inflammatory signals are largely unknown. Here, we report a previously unknown effect of basal autophagy. Lysosomal inhibition induced weak inflammatory signals in the absence of a cellular stimulus and in the presence of a nutrient supply, and their induction was impaired by MyD88 deficiency...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414768/gpatch3-negatively-regulates-rlr-mediated-innate-antiviral-responses-by-disrupting-the-assembly-of-visa-signalosome
#2
Ying Nie, Yong Ran, Hong-Yan Zhang, Zhe-Fu Huang, Zhao-Yi Pan, Su-Yun Wang, Yan-Yi Wang
Upon viral infection, retinoic acid-inducible gene I-like receptors (RLRs) recognize viral RNA and trigger a series of signaling events, leading to the induction of type I interferons (IFNs). These processes are delicately regulated to prevent excessive and harmful immune responses. In this study, we identified G patch domain-containing protein 3 (GPATCH3) as a negative regulator of RLR-mediated antiviral signaling pathways. Overexpression of GPATCH3 impaired RNA virus- triggered induction of downstream antiviral genes, whereas its knockdown had opposite effects and attenuated viral replication...
April 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410596/toll-like-receptor-4-in-glial-inflammatory-responses-to-air-pollution-in-vitro-and-in-vivo
#3
Nicholas C Woodward, Morgan C Levine, Amin Haghani, Farimah Shirmohammadi, Arian Saffari, Constantinos Sioutas, Todd E Morgan, Caleb E Finch
BACKGROUND: Exposure to traffic-related air pollution (TRAP) is associated with accelerated cognitive aging and higher dementia risk in human populations. Rodent brains respond to TRAP with activation of astrocytes and microglia, increased inflammatory cytokines, and neurite atrophy. A role for Toll-like receptor 4 (TLR4) was suggested in mouse TLR4-knockouts, which had attenuated lung macrophage responses to air pollution. METHODS: To further analyze these mechanisms, we examined mixed glial cultures (astrocytes and microglia) for RNA responses to nanoscale particulate matter (nPM; diameter <0...
April 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28404923/down-regulation-of-mir-146b-5p-by-long-noncoding-rna-malat1-in-hepatocellular-carcinoma-promotes-cancer-growth-and-metastasis
#4
Chao Li, Runchen Miao, Sushun Liu, Yong Wan, Simin Zhang, Yan Deng, Jianbin Bi, Kai Qu, Jingyao Zhang, Chang Liu
MicroRNAs play an important role in liver cancer genesis and progression. In this study, we identified down-regulation of miR-146b-5p associated with tumor growth, metastasis and poor survival in hepatocellular carcinoma (HCC) patients. miR-146b-5p could suppress proliferation, migration, and invasion and induced apoptosis in vitro and in vivo. Remarkably, TNF receptor associated factor 6 (TRAF6) was confirmed as a direct target of miR-146b-5p in HCC and miR-146b-5p exerted the tumor suppression roles through inhibiting the phosphorylation of Akt mediated by TRAF6...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404732/roles-of-the-traf6-and-pellino-e3-ligases-in-myd88-and-rankl-signaling
#5
Sam Strickson, Christoph H Emmerich, Eddy T H Goh, Jiazhen Zhang, Ian R Kelsall, Thomas Macartney, C James Hastie, Axel Knebel, Mark Peggie, Francesco Marchesi, J Simon C Arthur, Philip Cohen
It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is not essential for the IL-1-dependent formation of K63-Ub chains, TAK1 activation, or IL-8 production in human cells, because Pellino1 and Pellino2 generate the K63-Ub chains required for signaling in cells expressing E3 ligase-inactive TRAF6 mutants. The IL-1-induced formation of K63-Ub chains and ubiquitylation of IRAK1, IRAK4, and MyD88 was abolished in TRAF6/Pellino1/Pellino2 triple-knockout (KO) cells, but not in TRAF6 KO or Pellino1/2 double-KO cells...
April 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#6
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28393051/peroxiredoxin-6-negatively-regulates-bactericidal-activity-and-nf-%C3%AE%C2%BAb-activity-by-interrupting-traf6-ecsit-complex
#7
Yoon Min, Sae M Wi, Dongwoo Shin, Eunyoung Chun, Ki-Young Lee
A TRAF6-ECSIT complex is crucial for the generation of mitochondrial reactive oxygen species (mROS) and nuclear factor-kappa B (NF-κB) activation induced by Toll-like receptor 4 (TLR4). Peroxiredoxin-6 (Prdx6) as a member of the peroxiredoxin family of antioxidant enzymes is involved in antioxidant protection and cell signaling. Here, we report on a regulatory role of Prdx6 in mROS production and NF-κB activation by TLR4. Prdx6 was translocated into the mitochondria by TLR4 stimulation and Prdx6-knockdown (Prdx6(KD)) THP-1 cells had increased level of mitochondrial reactive oxygen species levels and were resistant to Salmonella typhimurium infection...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28380049/mir-144-attenuates-the-host-response-to-influenza-virus-by-targeting-the-traf6-irf7-signaling-axis
#8
Carrie M Rosenberger, Rebecca L Podyminogin, Alan H Diercks, Piper M Treuting, Jacques J Peschon, David Rodriguez, Madhumati Gundapuneni, Mitchell J Weiss, Alan Aderem
Antiviral responses must rapidly defend against infection while minimizing inflammatory damage, but the mechanisms that regulate the magnitude of response within an infected cell are not well understood. miRNAs are small non-coding RNAs that suppress protein levels by binding target sequences on their cognate mRNA. Here, we identify miR-144 as a negative regulator of the host antiviral response. Ectopic expression of miR-144 resulted in increased replication of three RNA viruses in primary mouse lung epithelial cells: influenza virus, EMCV, and VSV...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28378753/low-intensity-pulsed-ultrasound-lipus-prevents-periprosthetic-inflammatory-loosening-through-fbxl2-traf6-ubiquitination-pathway
#9
Xiang Zhao, Gangsheng Zhao, Zhongli Shi, Chenhe Zhou, Yunlin Chen, Bin Hu, Shigui Yan
Previous studies have shown that Low intensity pulsed ultrasound(LIPUS) prevents polyethylene-debris-induced periprosthetic loosening in vivo, but the details of the mechanism by which it does so remain unclear. In this article, we used polyethylene debris induced RAW 264.7 cells as the in vitro model, and tested the effect of LIPUS on this model. Changes in the level of inflammatory cytokines, cell proliferation, and apoptosis were assessed. Gene overexpression and siRNA technique were applied, and the levels of expression of FBXL2, TRAF6, ERK, and related inflammatory cytokines were also measured...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377715/protective-effects-of-dioscin-against-lipopolysaccharide-induced-acute-lung-injury-through-inhibition-of-oxidative-stress-and-inflammation
#10
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/28377308/cell-type-specific-regulatory-effects-of-glucocorticoids-on-cutaneous-tlr2-expression-and-signalling
#11
Qi Su, Anja Pfalzgraff, Günther Weindl
Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers. We found that Dex induced TLR2 expression mainly in undifferentiated and less in calcium-induced differentiated keratinocytes but not in HaCaT cells or fibroblasts, however, Dex reduced TLR1/6 expression...
April 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28377200/molecular-cloning-characterization-and-function-of-a-germinal-center-kinase-mst4-gene-from-litopenaeus-vannamei-in-response-to-vibrio-alginolyticus-challenge-in-tlr-traf6-signaling-pathway
#12
Chang-Sheng Zhao, Di Huang, Ting Peng, Ming-Zhu Huang, Chen-Ying Xie, Jun Chen, Jing-Rong Kong, Ren-Chong Xie, Yuan Liu, Wei-Na Wang
The serine/threonine protein kinase MST4 plays multiple roles in the regulation of signaling pathways that govern cellular processes including mitosis, migration, homeostasis, polarity, proliferation, differentiation and apoptosis. Here we report the identification and characterization of the full-length sequence of LvMST4 from the shrimp L. vannamei, and investigations into its role in the shrimp's immune response to infection by the pathogenic bacterium Vibrio alginolyticus. Subcellular localization assays demonstrated the enzyme's presence in the shrimp's cytoplasm, and tissue-specific expression analysis revealed that it is expressed ubiquitously but at different levels in different tissues...
April 6, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28372569/cancer-metastasis-issues-and-challenges
#13
EDITORIAL
Chao-Nan Qian, Yan Mei, Jian Zhang
Metastasis is the major cause of treatment failure in cancer patients and of cancer-related deaths. This editorial discusses how cancer metastasis may be better perceived and controlled. Based on big-data analyses, a collection of 150 important pro-metastatic genes was studied. Using The Cancer Genome Atlas datasets to re-analyze the effect of some previously reported metastatic genes-e.g., JAM2, PPARGC1A, SIK2, and TRAF6-on overall survival of patients with renal and liver cancers, we found that these genes are actually protective factors for patients with cancer...
April 3, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28357074/traf6-regulates-the-effects-of-polarized-maturation-of-tolerability-marrow-derived-dendritic-cells-on-collagen-induced-arthritis-in-mice
#14
Chenchen Zhuang, Xuezhi Hong, Jia Liu, Xiaohong Luo, Hanyou Mo
The study aimed to investigate the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and a differentially mature dendritic cell (mDC) in collagen-induced arthritis (CIA) mice and to determine whether or not TRAF6 regulates the activation of an immature dendritic cell (iDC) and inhibits iDC maturation to induce immune tolerance. The mouse bone marrow stem cells were induced with recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) to differentiate immature dendritic cells (DCs), which were divided into four groups with different maturation states: rmGM-CSF, rmIL-4; TNF-α; LPS; and FK506 group...
February 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28350111/melittin-inhibits-osteoclast-formation-through-the-downregulation-of-the-rankl-rank-signaling-pathway-and-the-inhibition-of-interleukin-1%C3%AE-in-murine-macrophages
#15
Jung-Yoon Choe, Seong-Kyu Kim
Melittin is a major toxic component of bee venom (Apis mellifera). It is not known whether melittin is involved in bone metabolism and osteoclastogenesis. The aim of this study was to determine the role of melittin in the regulation of osteoclastogenesis. In vitro osteoclastogenesis assays were performed using mouse RAW 264.7 cells and bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Morphologic and functional analyses for osteoclast-like multinucleated cells (MNCs) were performed by tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and pit formation methods...
February 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28341848/role-of-p62-in-the-suppression-of-inflammatory-cytokine-production-by-adiponectin-in-macrophages-involvement-of-autophagy-and-p21-nrf2-axis
#16
Nirmala Tilija Pun, Pil-Hoon Park
Adiponectin possesses potent anti-inflammatory properties. p62, an adaptor protein composed of multi-functional domain, is known to play a role in controlling inflammatory responses. In the present study, we examined the role of p62 in suppressing inflammatory cytokines produced by globular adiponectin (gAcrp) and the potential underlying mechanisms in macrophages. We demonstrated that gAcrp significantly increased p62 expression. Knockdown of p62 abrogated the suppressive effects of gAcrp on LPS-stimulated TNF-α and IL-1β expression and TRAF6/p38 MAPK pathway, indicating that p62 signaling is critical for suppressing inflammatory cytokines production by gAcrp...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338920/dendritic-cell-expression-of-the-signaling-molecule-traf6-is-required-for-immune-tolerance-in-the-lung
#17
Daehee Han, Matthew C Walsh, Kwang Soon Kim, Sung-Wook Hong, Junyoung Lee, Jaeu Yi, Gloriany Rivas, Yongwon Choi, Charles D Surh
Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung...
February 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28338190/the-role-of-mir-146a-in-modulating-traf6-induced-inflammation-during-lupus-nephritis
#18
C-Z Zheng, Y-B Shu, Y-L Luo, J Luo
OBJECTIVE: Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). A previous study showed decreased expression level of microRNA (miR)-146a in LN patients, indicating its possible role in LN pathogenesis. PATIENTS AND METHODS: A total of 98 LN patients were recruited, for the collection of renal tissue samples during biopsy or surgery. Another cohort of 15 patients who had renal tumor resection was recruited as the control group, for the further comparison of expression levels of miR-146a, TRAF6 and p-p65 in tissues...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28333374/odontoclastogenesis-of-mouse-papilla-derived-mdpc-23-cells-induced-by-lps
#19
C Li, W T Qi, H W Jiang
AIM: To investigate the role of LPS in the odontoclast differentiation of MDPC-23 cells. It was hypothesized that MDPC 23 odontoblast-like cells may function as odontoclasts under the influence of LPS. METHODOLOGY: MDPC-23 cells were cultured in the presence of 0.1 or 1 μg/mL LPS for 6 days. Cell viability was determined using the CCK8 assay. TRAP staining, dentine resorption assay and ROS detection by confocal laser scanning microscope were used to test the odontoclast-like function of the induced cells...
March 23, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28324845/pharmacological-effects-of-%C3%AE-d-mannuronic-acid-m2000-on-mir-146a-irak1-traf6-and-nf-%C3%AE%C2%BAb-gene-expression-as-target-molecules-in-inflammatory-reactions
#20
Seyed Shahabeddin Mortazavi Jahromi, Mehdi Malek Jamshidi, Ali Farazmand, Zahra Aghazadeh, Mehdi Yousefi, Abbas Mirshafiey
BACKGROUND: Impaired expression and function of microRNAs (miRNAs) are involved in the pathogenesis of many autoimmune and inflammatory diseases. Moreover, there is a close relationship between TLRs and miRNAs and impairment in regulating their expression which can play a vital role in the immunopathogenesis of many inflammatory reactions. This research aimed to study the pharmaceutical effects of M2000 (β-d-mannuronic acid) on the expression of miR-146a and its two target molecules (IRAK1 and TRAF6), and the transcription factor NF-κB in the HEK-Blue hTLR2 cell line...
January 24, 2017: Pharmacological Reports: PR
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