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interferon regulatory factor 7

Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
Wei-Shan Hung, Pin Ling, Ju-Chien Cheng, Shy-Shin Chang, Ching-Ping Tseng
Toll-like receptor 4 (TLR4) plays a pivotal role in the host response to lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria. Here, we elucidated whether the endocytic adaptor protein Disabled-2 (Dab2), which is abundantly expressed in macrophages, plays a role in LPS-stimulated TLR4 signaling and trafficking. Molecular analysis and transcriptome profiling of RAW264.7 macrophage-like cells expressing short-hairpin RNA of Dab2 revealed that Dab2 regulated the TLR4/TRIF pathway upon LPS stimulation...
October 17, 2016: Scientific Reports
Kwang-Soo Baek, Young-Su Yi, Young-Jin Son, Sulgi Yoo, Nak Yoon Sung, Yong Kim, Sungyoul Hong, Adithan Aravinthan, Jong-Hoon Kim, Jae Youl Cho
BACKGROUND: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. METHODS: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography...
October 2016: Journal of Ginseng Research
Yang Zhao, Wenxia Chen, Weiliang Zhu, Hui Meng, Jie Chen, Jian Zhang
The purpose of this study was to identify the role of interferon regulatory factor 7 (IRF7) in the bone metastasis of prostate cancer. Herein, we demonstrated the lower expression of IRF7 in bone metastases of prostate cancer. Overexpression of IRF7 in prostate cancer cells had a marked effect on inhibiting bone metastases but not on tumor growth in xenograft nude mice. While in vitro, up-regulation of IRF7 had little effect on the malignant phenotype of prostate cancer cells including proliferation, apoptosis, migration, and invasion...
October 11, 2016: Oncology Research
Ning Li, Tianqi Hong, Rong Li, Yao Wang, Mengjiao Guo, Zongxi Cao, Yumei Cai, Sidang Liu, Tongjie Chai, Liangmeng Wei
Mitochondrial antiviral-signaling protein (MAVS), an adaptor protein of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated signal pathway, is involved in innate immunity. In this study, Cherry Valley duck MAVS (duMAVS) was cloned from the spleen and analyzed. duMAVS was determined to have a caspase activation and recruitment domain at N-terminal, followed by a proline-rich domain and a transmembrane domain at C-terminal. Quantitative real-time PCR indicated that duMAVS was expressed in all tissues tested across a broad expression spectrum...
2016: Frontiers in Immunology
Musheng Bao, York Wang, Ying Liu, Peiqing Shi, Hongbo Lu, Wenwen Sha, Leiyun Weng, Shino Hanabuchi, Jun Qin, Joel Plumas, Laurence Chaperot, Zhiqiang Zhang, Yong-Jun Liu
Plasmacytoid dendritic cells (pDCs) rapidly produce large amounts of type 1 interferon (IFN) after Toll-like receptor 7 and 9 engagements. This specialized function of type 1 IFN production is directly linked to the constitutive expression of IRF7, the master transcription factor for type 1 IFN production. However, the IRF7 regulatory network in pDCs remains largely unknown. In this study, we identify that the transcription factor NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production. Furthermore, knockout of NFATC3 greatly reduced the CpG DNA-induced nuclear translocation of IRF7, which resulted in impaired type 1 IFN production in vitro and in vivo...
October 3, 2016: Journal of Experimental Medicine
Zacharey Guinn, Anna T Lampe, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF)3 is a crucial transcription factor during innate immune responses. Here we show IRF3 also has a role in adaptive T cell immune responses. Expression of IFN-γ, IL-17, and Granzyme B (GrB) during in vitro T cell responses was impaired when either dendritic cells (DCs) or T cells were derived from IRF3KO mice. Unexpectedly, IRF3-dependent NK-activating molecule (INAM), which is an NK cell activating factor of the DC innate immune response, was induced during the T cell response...
September 4, 2016: Cellular Immunology
Sathish Kumar Maney, Haifeng C Xu, Jun Huang, Aleksandra A Pandyra, Christian Ehlting, Renan Aguilar-Valenzuela, Vitaly I Pozdeev, David R McIlwain, Albert Zimmermann, Johannes G Bode, Hartmut Hengel, Carsten J Kirschning, Ira R Kim, John Hiscott, Dirk Brenner, Dieter Häussinger, Pamela S Ohashi, Tak W Mak, Karl S Lang, Philipp A Lang
BACKGROUND/AIMS: Viral infections represent a global health problem with the need for new viral therapies and better understanding of the immune response during infection. The most immediate and potent anti-viral defense mechanism is the production of type I interferon (IFN-I) which are activated rapidly following recognition of viral infection by host pathogen recognition receptors (PRR). The mechanisms of innate cellular signaling downstream of PRR activation remain to be fully understood...
2016: Cellular Physiology and Biochemistry
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
Hirotomo Nakaoka, Masaki Mogi, Jun Suzuki, Harumi Kan-No, Li-Juan Min, Jun Iwanami, Masatsugu Horiuchi
We previously reported interferon regulatory factor (IRF) 1 plays physiological roles in "growth"-regulated angiotensin II type 2 (AT2) receptor expression in fibroblasts. Here, we investigated whether IRF-1 is involved in attenuation of vascular remodeling in association with AT2 receptor upregulation. Neointimal area in injured artery after 14 days of cuff placement was significantly increased in IRF-1 knockout mice (IRF-1KO) and AT2 receptor knockout mice (AT2KO) compared with wild-type mice (WT: C57BL/6J)...
October 2016: Journal of the American Society of Hypertension: JASH
Ying-Hsien Huang, Hsiang-Hung Shih, Mao-Meng Tiao, Chao-Cheng Huang, Kuang-Che Kuo, Fu-Chen Huang, Ya-Ling Yang, Jiin-Haur Chuang
BACKGROUND/PURPOSE: Viral infections and innate immunity signaling, especially Toll-like receptor 7 (TLR7) have been implicated in the pathogenesis of biliary atresia (BA). Administration of rhesus rotavirus-type A to newborn Balb/c mice produces inflammatory obstruction of bile ducts, which resembles human BA. However, whether activation of TLR7 signaling plays a role in neonatal hepatobiliary injury remains to be investigated. METHODS: TLR7 agonist, imiquimod (R837), was intraperitoneally administered to Balb/c mice within 24 hours of birth and then every other day...
August 3, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Stephen R Koch, Fred S Lamb, Judith Hellman, Edward R Sherwood, Ryan J Stark
Repeated challenge of lipopolysaccharide (LPS) alters the response to subsequent LPS exposures via modulation of toll-like receptor 4 (TLR4). Whether activation of other TLRs can modulate TLR4 responses, and vice versa, remains unclear. Specifically with regards to endothelial cells, a key component of innate immunity, the impact of TLR cross-modulation is unknown. We postulated that TLR2 priming (via Pam3Csk4) would inhibit TLR4-mediated responses while TLR3 priming (via Poly I:C) would enhance subsequent TLR4-inflammatory signaling...
August 8, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
G V Seledtsova, A A Shishkov, E A Kaschenko, V I Seledtsov
An accumulating body of evidence suggests that xenogeneic vaccines can be very effective in breaking the immune tolerance to human tumor-associated antigens (TAAs). We assessed adverse effects, as well as clinical and immune responses induced by a lyophilized xenogeneic polyantigenic vaccine (XPV) prepared from murine melanoma B16 and carcinoma LLC cells in 60 stage IV colorectal cancer patients. Neither grade III/IV toxicities, nor laboratory and clinical signs of systemic severe autoimmune disorders were documented in any XPV-treated patient...
August 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Keishi Tanigawa, Yusuke Itoh, Yasunobu Kobayashi
Context • Combined treatment with an extract of Lentinula edodes mycelia (LEM) and chemotherapy has been reported to improve quality of life (QOL) and immunological function in cancer patients. However, those effects have not been elucidated for patients receiving cancer immunotherapy. Objective • The present study intended to investigate the effects of oral LEM on QOL and immunological function in cancer patients receiving immunotherapy. Design • The research team designed an open-label, single-armed pilot study...
July 2016: Alternative Therapies in Health and Medicine
B Imko-Walczuk, M L Piesiaków, P Trzonkowski, M Pikuła, A Dębska-Ślizień, B Rutkowski
INTRODUCTION: Skin malignancies are the most prevalent neoplasms seen in organ transplant recipients (OTRs). Immunosuppressive treatment has been attributed to play a causative role in malignancy development. The aim of the study was to assess cytokine concentrations involved in cytotoxic and regulatory responses in patients after organ transplantation (Tx). We compared two OTR subgroups: those with malignant skin tumors and those without any known changes developed after Tx. MATERIALS AND METHODS: We enrolled 102 patients, 63: 3-360 (median: min-max) months after Tx, aged 54...
June 2016: Transplantation Proceedings
W W Li, P Sun, D D Chen, W Q Wang, G H Jiao, Y J Wang, L Zhou, B M Wang, J Zhang
OBJECTIVE: To investigate the preventive and therapeutic effects of rapamycin (RAPA) on autoimmune hepatitis and liver fibrosis induced by concanavalin A (ConA) and possible mechanisms. METHODS: Female C57BL/6 mice aged 8 weeks were randomly divided into normal control group, ConA model group, and ConA+RAPA treatment group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured; hematoxylin-eosin and Masson staining and Knodell HAI and Ishak scoring systems were used to evaluate the degrees of liver inflammation and fibrosis...
May 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Ling Wang, Juan Zhao, Junping Ren, Kenton H Hall, Jonathan P Moorman, Zhi Q Yao, Shunbin Ning
Interferon (IFN) regulatory factor 7 (IRF7) plays a key role in the production of IFN-α in response to viral infection, and phosphorylation at IRF7 C-terminal serine sites is prelude to its function. However, phosphatases that negatively regulate IRF7 phosphorylation and activity have not been reported. In this study, we have identified a conserved protein phosphatase 1 (PP1)-binding motif in human and mouse IRF7 proteins, and shown that PP1 physically interacts with IRF7. Exogenous expression of PP1 subunits (PP1α, β, or γ) ablates IKKε-stimulated IRF7 phosphorylation and dramatically attenuates IRF7 transcriptional activity...
October 2016: European Journal of Immunology
Lisbeth Ramírez-Carvajal, Fayna Diaz-San Segundo, Elizabeth Ramirez-Medina, Luis L Rodríguez, Teresa de Los Santos
UNLABELLED: Foot-and-mouth disease (FMD) remains one of the most devastating livestock diseases around the world. Several serotype-specific vaccine formulations exist, but they require about 5 to 7 days to induce protective immunity. Our previous studies have shown that a constitutively active fusion protein of porcine interferon (IFN) regulatory factors (IRF) 7 and 3 [IRF7/3(5D)] strongly induced type I IFN and antiviral genes in vitro and prevented mortality in an FMD mouse model when delivered with a replication-defective adenoviral vector [Ad5-poIRF7/3(5D)]...
October 1, 2016: Journal of Virology
Hai-Bo Tang, Zhuan-Ling Lu, Xian-Kai Wei, Tao-Zhen Zhong, Yi-Zhi Zhong, Ling-Xuan Ouyang, Yang Luo, Xing-Wei Xing, Fang Liao, Ke-Ke Peng, Chao-Qian Deng, Nobuyuki Minamoto, Ting Rong Luo
Viperin (virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible) is an interferon-inducible protein that mediates antiviral activity. Generally, rabies virus (RABV) multiplies extremely well in susceptible cells, leading to high virus titres. In this study, we found that viperin was significantly up-regulated in macrophage RAW264.7 cells but not in NA, BHK-21 or BSR cells. Transient viperin overexpression in BSR cells and stable expression in BHK-21 cells could inhibit RABV replication, including both attenuated and street RABV...
2016: Scientific Reports
Inna G Ovsyannikova, Ann L Oberg, Richard B Kennedy, Michael T Zimmermann, Iana H Haralambieva, Krista M Goergen, Diane E Grill, Gregory A Poland
To assess gene signatures related to humoral response among healthy older subjects following seasonal influenza vaccination, we studied 94 healthy adults (50-74 years old) who received one documented dose of licensed trivalent influenza vaccine containing the A/California/7/2009 (H1N1)-like virus strain. Influenza-specific antibody (HAI) titer in serum samples and next-generation sequencing on PBMCs were performed using blood samples collected prior to (Day 0) and at two timepoints after (Days 3 and 28) vaccination...
May 2016: Heliyon
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