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Lorena P Suarez-Kelly, Gregory M Kemper, Megan C Duggan, Andrew Stiff, Tiffany C Nole, Joseph Markowitz, Eric A Luedke, Vedat O Yildiz, Lianbo Yu, Alena Cristina Jaime-Ramirez, Volodymyr Karpa, Xiaoli Zhang, William E Carson
The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed...
October 21, 2016: Oncotarget
Cinthia C Stempin, Claudia C Motrán, María P Aoki, Cristian R Falcón, Fabio M Cerbán, Laura Cervi
Macrophage plasticity is critical for controlling inflammation including those produced by helminth infections, where alternatively activated macrophages (AAM) are accumulated in tissues. AAM expressing the co-inhibitory molecule programmed death ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasitic infections. However, the role of PD-L2 during F. hepatica infection has not yet been explored. We observed that F. hepatica infection or a F...
October 21, 2016: Oncotarget
Laura Denise Mendes da Silva, Mariana Gatto, Mariana Miziara de Abreu Teodoro, Marjorie de Assis Golim, Érika Alessandra Pelisson Nunes da Costa, Francilene Capel Tavares Carvalho, Daniela Ramos Rodrigues, Paulo Câmara Marques Pereira, Ângela Maria Victoriano de Campos Soares, Sueli Aparecida Calvi
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30 to 40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury...
October 26, 2016: Scandinavian Journal of Immunology
Huib H Rabouw, Martijn A Langereis, Robert C M Knaap, Tim J Dalebout, Javier Canton, Isabel Sola, Luis Enjuanes, Peter J Bredenbeek, Marjolein Kikkert, Raoul J de Groot, Frank J M van Kuppeveld
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I interferon (IFN-α/β) response, the protein kinase R (PKR)-mediated stress response is being recognized as an important innate response pathway. Upon detecting viral dsRNA, PKR phosphorylates eIF2α, leading to the inhibition of cellular and viral translation and the formation of stress granules (SGs), which are increasingly recognized as platforms for antiviral signaling pathways...
October 2016: PLoS Pathogens
Thierry Lioux, Marc-Antoine Mauny, Alain Lamoureux, Nicolas Bascoul, Mathieu Hays, Fabienne Vernejoul, Anne-Sophie Baudru, Cédric Boularan, Justine Lopes-Vicente, Gregory Qushair, Gérard Tiraby
We describe novel STING-activating cyclic dinucleotides whose constituent nucleosides are adenosine and inosine, and that vary by ribose substitution, internucleotide linkage position and phosphate modification. In mammalian cells in vitro, some of these cAIMP analogs induce greater STING-dependent IRF and NF-κB pathway signaling than do the reference agonists for murine (DMXAA) or human (2',3'-cGAMP) STING. In human blood ex vivo, they induce type I interferons (IFNs) and pro-inflammatory cytokines: for the former, 3',3'-cAIMP (9; EC50: 6...
October 26, 2016: Journal of Medicinal Chemistry
Sara De Biasi, Elena Bianchini, Milena Nasi, Margherita Digaetano, Lara Gibellini, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Marcello Pinti, Cristina Mussini, Andrea Cossarizza
INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients. METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR)...
November 13, 2016: AIDS
Paola Triggianese, Paola Conigliaro, Maria Sole Chimenti, Livia Biancone, Giovanni Monteleone, Roberto Perricone, Ivan Monteleone
OBJECTIVES: Both the innate and the adaptive immune responses contribute to the onset of chronic inflammation in spondyloarthritis (SpA). The association between SpA and inflammatory bowel disease (IBD, enteropathic SpA-ESpA) has been largely established and suggests a shared pathophysiology. There is evidence that innate lymphoid cells (ILC) are involved in the pathogenesis of both SpA and IBD while no evidence has been reported to date on ESpA. We aimed to analyse for the first time the frequency and cytokine expression of ILC in peripheral blood from ESpA patients compared with both IBD and healthy subjects...
October 21, 2016: Clinical and Experimental Rheumatology
Soodabeh Iranpour, Vahid Nejati, Nowruz Delirezh, Pouria Biparva, Sadegh Shirian
BACKGROUND: Developing safe and effective cancer vaccine formulations is a primary focus in the field of cancer immunotherapy. Dendritic cells (DC) are currently employed as cellular vaccine in clinical trials of tumor immunotherapy. Recognizing the critical role of DCs in initiating anti-tumor immunity has resulted in the development of several strategies that target vaccine antigens to DCs to trigger anti-tumor T cell responses. To increase the efficiency of antigen delivery systems for anti-tumor vaccines, encapsulation of tumor-associated antigens in polymer nanoparticles (NPs) has been established...
October 26, 2016: Journal of Experimental & Clinical Cancer Research: CR
Wen Gu, Rong Cui, Tao Ding, Xiaoming Li, Juan Peng, Weiguo Xu, Fengfeng Han, Xuejun Guo
BACKGROUND AND OBJECTIVE: Statins have been widely used in inflammatory diseases including asthma, because of their anti-inflammatory and immunomodulatory properties. It has been shown that simvastatin induces autophagy and cell death in some circumstances. However, the possible cross-talk between simvastatin and autophagic processes in lung disease is largely unknown. Thus, we investigated the impact of simvastatin on airway inflammation and airway remodelling and the possible relationship of these processes to a simvastatin-induced autophagic pathway in mouse models of asthma...
October 26, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Sajith Nair, Pradeep Bist, Neha Dikshit, Manoj N Krishnan
Type I interferon (IFN-I) mediated innate immune response controls virus infections by inducing the expression of interferon stimulated genes (ISGs). Although ubiquitination plays key roles in immune signaling regulation, a human genome-wide understanding of the role of E3 ubiquitin ligases in interferon mediated ISG induction is lacking. Here, we report a genome-wide profiling of the effect of ectopic expression of 521 E3 ubiquitin ligases and substrate recognition subunits encoded in the human genome (which constitutes 84...
October 26, 2016: Scientific Reports
Yang Yu, Yan Liu, Chen Zong, Qingbo Yu, Xue Yang, Lei Liang, Fei Ye, Li Nong, Yuxian Jia, Yongkui Lu, Zhipeng Han
Mesenchymal stem cells (MSCs) are generally used in regenerative medicine, tissue engineering and therapy for immune disorder diseases. However, due to the immunosuppressive function of MSCs, the application of MSCs in breast cancer therapy remains limited. Sirt1 is the closest mammalian homologue of the yeast enzyme Sir2 which has an established capacity to influence yeast replicative lifespan. In this study, we demonstrated the effect of MSCs with Sirt1 overexpression (MSCs-Sirt1) in mice bearing 4T1 breast cancer and investigated the underlying mechanism...
October 26, 2016: Scientific Reports
Kai Wang, Feng Jin, Zhanpu Zhang, Xiaochuan Sun
BACKGROUND Specific T cell phenotype has been reported to potentially contribute to the development of angiotensin II (Ang II)-induced several vascular disorders. Type 2 diabetes mellitus (T2DM) is intimately associated with cardiovascular disease. The present study aimed to investigate the relationship between T cell phenotypes and Ang II in T2DM patients combined with carotid atherosclerosis (CA). MATERIAL AND METHODS This study was performed on 50 patients with T2DM in our hospital. Based on the presence of CA, they were divided into CA group (presence of CA, n=30) or T2DM group (absence of CA, n=20)...
October 26, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jolene Carlson, Vivian O'Donnell, Marialexia Alfano, Lauro Velazquez Salinas, Lauren G Holinka, Peter W Krug, Douglas P Gladue, Stephen Higgs, Manuel V Borca
African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated...
October 22, 2016: Viruses
Kelly C G Manfrere, Marina P Torrealba, Denis R Miyashiro, Luanda M S Oliveira, Gabriel C de Carvalho, Josenilson F Lima, Anna Claudia C C Branco, Nátalli Z Pereira, Juliana Pereira, José A Sanches, Maria N Sato
Sézary syndrome (SS) carries a poor prognosis, and infections represent the most frequent cause of death in SS patients. Toll-like receptors (TLRs) are a family of innate immune receptors that induce protective immune responses against infections. We sought to evaluate the ability of TLR agonists to induce inflammatory cytokine, Th2 cytokine, and type I interferon (IFN-I) production by peripheral blood mononuclear cells (PBMC) of untreated SS patients. We detected impaired IL-6, IL-10 and IL-13 secretion by PBMC induced by the agonists for TLR5, TLR3, TLR7 and TLR9 in SS patients, while it was partially recovered by TLR2/TLR4 and TLR7/8 agonists TNF secretion was restored following stimulation with TLR2/TLR4 agonists...
October 21, 2016: Oncotarget
Zhen Gan, Shan Nan Chen, Bei Huang, Jing Hou, Pin Nie
Type I IFNs are considered to be the core IFN species in vertebrates because of their predominant antiviral effects. But, a puzzling question remains to be answered, as to how intronless type I IFN genes in amniotes might have evolved from intron-containing type I IFN genes in fish and amphibians. In this study, intronless and intron-containing type I IFNs were found in the amphibian model, Xenopus tropicalis, with a total of sixteen and five genes, respectively. The intronless IFNs can be divided into three subgroups, and the intron-containing ones into two subgroups, implying that a retroposition event might have occurred in amphibians, resulting in the generation of intronless type I IFN genes...
October 22, 2016: Developmental and Comparative Immunology
Xing He, Rui Tang, Yue Sun, Yan-Ge Wang, Kui-Yang Zhen, Dong-Mei Zhang, Wei-Qing Pan
Schistosomiasis is a chronic disease caused by the parasite of the Schistosoma genus and is characterized by egg-induced hepatic granulomas and fibrosis. Macrophages play a central role in schistosomiasis with several studies highlighting their differentiation into M2 cells involved in the survival of infected mice through limitation of immunopathology. However, little is known regarding the mechanisms of regulating macrophage differentiation. Here, we showed that the early stage of infection by Schistosoma japonicum induced expression of type 1T-helper-cell (Th1) cytokine, interferon-γ (IFN-γ), leading to increase in M1 cells...
October 19, 2016: EBioMedicine
Yu-Han Meng, Xiao-Hui Zhu, Li-Ying Yan, Yan Zhang, Hong-Yan Jin, Xi Xia, Rong Li, Jie Qiao
INTRODUCTION: The successful pregnancy depends on maternal immune tolerance against the fetus. It has been reported that MSCs (mesenchymal stem cells) could play a regulatory role on immune cells such as CD4(+)T cells, macrophages and NK cells, but their effect on recurrent miscarriage is unknown. STUDY DESIGN: In a prospective study, the abortion-prone (CBA/J × DBA/2) H-2(d) × H-2(k) mice were utilized. Female CBA/J mice (8-10 weeks old) were injected with vehicle or MSCs via tail vein or uterine horns, and 14 days later, they were mated with DBA/2 males for the following experiments...
November 2016: Placenta
Johnathan Ho, Christin Pelzel, Andreas Begitt, Maureen Mee, Hany M Elsheikha, David J Scott, Uwe Vinkemeier
STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here, we show that STAT2 constitutively bound to STAT1, but not STAT3, via a conserved interface. While this interaction was irrelevant for type 1 interferon signaling and STAT1 activation, it precluded the nuclear translocation specifically of STAT1 in response to IFN-γ, interleukin-6 (IL-6), and IL-27...
October 2016: PLoS Biology
Yu Wu, Bin Yue, Jia Liu
Obesity is characterized by the abnormal or excessive fat accumulation that may impair health and extensive increase in body mass index (BMI). Childhood obesity may occur due to disturbances in metabolic regulation, which lead to metabolic syndrome and other diseases. Peripheral blood suspended immune cells are responsible for immune surveillance. The aim of the present study was to map the inflammatory cytokine expression pattern of isolated peripheral blood mononuclear cells (PBMCs) following lipopolysaccharide (LPS) stress in vitro and clinical chemistry parameters in the plasma of subjects...
October 20, 2016: Molecular Medicine Reports
Lun Cai, Lei Yu, Sa Liu, Tongxun Li, Xiaoping Zhang, Wei Cui, Jie Du, Qinyi Zhang
Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n = 18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8- NKT cell subsets (8...
October 24, 2016: Inflammation
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