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https://www.readbyqxmd.com/read/29458011/inflammatory-cytokines-induce-podoplanin-expression-at-the-tumor-invasive-front
#1
Akiko Kunita, Vanessa Baeriswyl, Claudia Meda, Erik Cabuy, Kimiko Takeshita, Enrico Giraudo, Andreas Wicki, Masashi Fukayama, Gerhard Christofori
Tumor invasion is a critical first step in the organismic dissemination of cancer cells and the formation of metastasis in distant organs, the most important prognostic factor and the actual cause of death in most of the cancer patients. We report here that the cell surface protein podoplanin (PDPN), a potent inducer of cancer cell invasion, is conspicuously expressed by the invasive front of squamous cell carcinomas (SCC) of the cervix in patients and in the transgenic HPV/E2 mouse model of cervical cancer...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29453519/tricurin-a-synergistic-formulation-of-curcumin-resveratrol-and-epicatechin-gallate-repolarizes-tumor-associated-macrophages-and-triggers-an-immune-response-to-cause-suppression-of-hpv-tumors
#2
Sumit Mukherjee, Rahman Hussaini, Richard White, Doaa Atwi, Angela Fried, Samay Sampat, Longzhu Piao, Quintin Pan, Probal Banerjee
Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells. Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell-implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell Carcinoma (HNSCC) cells in nude/nude mice...
February 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29449061/c4a-mrna-expression-in-pbmcs-predicts-the-presence-and-severity-of-delusions-in-schizophrenia-and-bipolar-disorder-with-psychosis
#3
Jennifer K Melbourne, Cherise Rosen, Benjamin Feiner, Rajiv P Sharma
Altered immune function is an established finding in psychotic disorders such as schizophrenia and bipolar disorder with psychosis, though its role in their development and progression remains to be understood. Evidence suggests altered JAK-STAT1 pathway activity in peripheral blood cells from participants with schizophrenia compared to controls. Activation of this pathway leads to increased expression of complement component 4A (C4A), which has recently been implicated in schizophrenia. Here, we examine mRNA expression of C4A in peripheral blood cells from participants with schizophrenia, bipolar disorder and controls...
February 12, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29446489/alcohol-attenuates-anti-hcv-function-of-ifn-%C3%AE-1-through-up-regulation-of-plasy-expression-in-human-hepatic-cells
#4
Meihua Ran, Jiegang Huang, Hao Liang, Junjun Jiang, Bingyu Liang, Chuanyi Ning, Ning Zang, Weibo Liao, Huifang Liu, Fengxiang Qin, Quanlue Yang, Wenzhe Ho, Li Ye, Hui Chen
AIM: Alcohol could compromise the anti-hepatitis C virus (HCV) function of interferon-alpha (IFN-α). However, little information is available about the effect of alcohol on interferon-lambda (IFN-λ, type III IFN), a novel candidate for development of therapy for HCV infection. METHODS: Huh7 cells were infected with HCV JFH-1 virus, then treated with alcohol and/or IFN-λ1. RT-PCR and western blot were used to detect the levels of HCV and key cellular factors. Overexpression or silencing expression was performed to verify the role of key factors in alcohol-attenuated anti-HCV function of IFN-λ1...
February 15, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29443928/changes-in-the-anti-allergic-activities-of-sesame-by-bioconversion
#5
Tae-Dong Jung, Sun-Il Choi, Seung-Hyun Choi, Bong-Yeon Cho, Wan-Sup Sim, Sang Jong Lee, Seon Ju Park, Dan-Bi Kim, Young-Cheul Kim, Jin-Ha Lee, Ok-Hwan Lee
Sesame is an important oilseed crop, which has been used as a traditional health food to ameliorate the prevention of various diseases. We evaluated the changes in the anti-allergic activities of sesame by bioconversion. SDS-PAGE of non-fermented sesame proteins showed major allergen bands, while that of fermented sesame showed only a few protein bands. Additionally, we investigated the effectiveness of fermented sesame by bioconversion in tumor necrosis factor-α (TNF-α)- and interferon-γ (IFN-γ)-induced HaCaT cells...
February 14, 2018: Nutrients
https://www.readbyqxmd.com/read/29443378/hepatitis-c-virus-e2-envelope-glycoprotein-induces-an-immunoregulatory-phenotype-in-macrophages
#6
Young-Chan Kwon, Keith Meyer, Guangyong Peng, Soumya Chatterjee, Daniel F Hoft, Ranjit Ray
A comprehensive strategy to control HCV infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 EnvGPs as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte derived macrophages as antigen presenting cells. HCV E2 induced immune regulatory cytokine IL-10 and sCD163 protein expression in macrophages from 7 of 9 blood donors tested. Further, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization towards M2 phenotype...
February 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29441069/interleukin-6-and-interferon-%C3%AE-signaling-via-jak1-stat-differentially-regulate-oncolytic-versus-cytoprotective-antiviral-states
#7
Oded Danziger, Tal Pupko, Eran Bacharach, Marcelo Ehrlich
Malignancy-induced alterations to cytokine signaling in tumor cells differentially regulate their interactions with the immune system and oncolytic viruses. The abundance of inflammatory cytokines in the tumor microenvironment suggests that such signaling plays key roles in tumor development and therapy efficacy. The JAK-STAT axis transduces signals of interleukin-6 (IL-6) and interferons (IFNs), mediates antiviral responses, and is frequently altered in prostate cancer (PCa) cells. However, how activation of JAK-STAT signaling with different cytokines regulates interactions between oncolytic viruses and PCa cells is not known...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29437254/crispr-cas9-knockout-of-usp18-enhances-type-i-ifn-responsiveness-and-restricts-hiv-1-infection-in-macrophages
#8
Jared P Taylor, Melanie N Cash, Katherine E Santostefano, Mahito Nakanishi, Naohiro Terada, Mark A Wallet
The IFN-stimulated gene ubiquitin-specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFN-α receptor 2 subunit (IFNAR2). Here, we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN-dependent manner. Experimental depletion of USP18 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model...
February 13, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29434310/recombinant-ifn-%C3%AE-from-the-bank-vole-myodes-glareolus-a-novel-tool-for-research-on-rodent-reservoirs-of-zoonotic-pathogens
#9
Francesca Torelli, Steffen Zander, Heinz Ellerbrok, Georg Kochs, Rainer G Ulrich, Christian Klotz, Frank Seeber
Rodent species like Myodes glareolus and Microtus spp. are natural reservoirs for many zoonotic pathogens causing human diseases and are gaining increasing interest in the field of eco-immunology as candidate animal models. Despite their importance the lack of immunological reagents has hampered research in these animal species. Here we report the recombinant production and functional characterization of IFN-γ, a central mediator of host's innate and adaptive immune responses, from the bank vole M. glareolus...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29427792/s-glutathionylation-exerts-opposing-roles-in-the-regulation-of-stat1-and-stat3-signaling-in-reactive-microglia
#10
Elena Butturini, Flora Cozzolino, Diana Boriero, Alessandra Carcereri de Prati, Maria Monti, Michele Rossin, Diana Canetti, Barbara Cellini, Piero Pucci, Sofia Mariotto
STAT1 and STAT3 are two transcription factors involved in a lot of cellular functions such as immune response, proliferation, apoptosis, and cell survival. A number of literature evidences described a yin-yang relationship between activation of STAT1 and STAT3 in neurodegenerative disorders where STAT1 exerts a pro-apoptotic effect whereas STAT3 shows neuroprotective properties through the inhibition of apoptosis. Although the role of oxidative-stress in the pathogenesis of neurodegeneration is clearly described, its influence in the regulation of these pathways is poorly understood...
February 7, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29424313/mesenchymal-stem-cells-inhibited-dendritic-cells-via-the-regulation-of-stat1-and-stat6-phosphorylation-in-experimental-autoimmune-uveitis
#11
L Dong, X Chen, H Shao, L Bai, X Li, X Zhang
PURPOSE: We have previously reported that MSCs inhibited experimental autoimmune uveitis (EAU) in rodent models induced by either uveitogenic antigens or antigen-specific T cells. In this study, we explored the inhibitory mechanisms of MSCs on dendritic cells (DCs) in EAU. METHODS: We collected the DCs from the lymph nodes of MSC treated or untreated EAU rats, as well as bone marrow derived DCs cultured in vitro with or without MSC treatment. The levels of costimulatory molecules of CD80, CD86, CD40, OX40L and suppressors of cytokine signaling (SOCS1, SOCS2, and SOCS3) on these DCs were analyzed by flow Cytometry...
February 7, 2018: Current Molecular Medicine
https://www.readbyqxmd.com/read/29421237/silencing-of-long-isoforms-of-nuclear-factor-erythroid-2-like-1-primes-macrophages-towards-m1-polarization
#12
Huihui Wang, Jiayu Zhu, Zhiyuan Liu, Hang Lv, Peng Lv, Feng Chen, Jingqi Fu, Yongyong Hou, Rui Zhao, Yuanyuan Xu, Qiang Zhang, Jingbo Pi
Macrophages are a major component of the immune system and play an important role in regulating the magnitude, duration, and quality of the inflammatory response. Dissecting the functions of transcription factors regulating macrophage activation is important for understanding the inflammatory responses. Nuclear factor erythroid 2 like 1 (NFE2L1, also known as Nrf1) is a CNC-bZIP protein, which has multiple isoforms. While the exact physiological functions of various isoforms of NFE2L1 are still under investigation, accumulating evidence indicate that long isoforms of NFE2L1 (NFE2L1(L)) are important regulators in the antioxidant response, proteasome homeostasis and inflammation...
February 2, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29419930/stat1-is-a-sex-specific-tumor-suppressor-in-colitis-associated-colorectal-cancer
#13
Ilija Crnčec, Madhura Modak, Claire Gordziel, Jasmin Svinka, Irene Scharf, Stefan Moritsch, Paulina Pathria, Michaela Schlederer, Lukas Kenner, Gerald Timelthaler, Mathias Müller, Birgit Strobl, Emilio Casanova, Editha Bayer, Thomas Mohr, Johannes Stöckl, Karlheinz Friedrich, Robert Eferl
The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1 ∆ IEC ). Male but not female STAT1 ∆ IEC mice were more resistant to DSS-induced colitis than sex-matched STAT1 flox/flox controls and displayed reduced intraepithelial infiltration of CD8 + TCRαβ + Granzyme B + T cells. Moreover, DSS treatment failed to induce expression of T cell-attracting chemokines in intestinal epithelial cells of male but not of female STAT1 ∆ IEC mice...
February 8, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29417693/mutations-in-the-stat-family-of-genes-in-cancer
#14
REVIEW
Nahid Shahmarvand, Alexandra Nagy, Jahanbanoo Shahryari, Robert S Ohgami
In recent years, it has become clear that members of the signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. The STAT family consists of six genes, STAT1-4, STAT5A/ STAT5B and STAT6, that are involved in regulating cellular proliferation, apoptosis, angiogenesis and the immune system response. Constitutive activation of STAT3, via mutational changes, has been shown to be important in oncogenesis in both solid and hematopoietic cancers. In the case of hematopoietic neoplasms, STAT3 driver mutations have been described in T-cell large granular lymphocytic leukemia (T-LGL) and chronic natural killer lymphoproliferative disorders (CLPD-NK) and are seen in 30-40% of T-LGL patients...
February 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29417241/myxovirus-resistance-protein-a-inhibits-hepatitis-c-virus-replication-through-jak-stat-pathway-activation
#15
Hailong Wang, Xiu Xin, Mingzhen Wang, Lingling Han, Jiadai Li, Yao Hao, Congyi Zheng, Chao Shen
The interferon-inducible dynamin-like GTPase myxovirus resistance protein A (MxA) exhibits activity against multiple viruses. However, its role in the life cycle of hepatitis C virus (HCV) is unclear, and the mechanisms underlying the anti-HCV activity of MxA require further investigation. In this study, we demonstrated that exogenous MxA expression in the Huh7 and Huh7.5.1 hepatoma cell lines significantly decreased the levels of HCV RNA and core proteins, whereas MxA knockdown exerted the opposite effect...
February 7, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29417186/a-type-1-diabetes-genetic-risk-score-can-discriminate-monogenic-autoimmunity-with-diabetes-from-early-onset-clustering-of-polygenic-autoimmunity-with-diabetes
#16
Matthew B Johnson, Kashyap A Patel, Elisa De Franco, Jayne A L Houghton, Timothy J McDonald, Sian Ellard, Sarah E Flanagan, Andrew T Hattersley
AIMS/HYPOTHESIS: Identifying individuals suitable for monogenic autoimmunity testing and gene discovery studies is challenging: early-onset type 1 diabetes mellitus can cluster with additional autoimmune diseases due to shared polygenic risk and islet- and other organ-specific autoantibodies are present in both monogenic and polygenic aetiologies. We aimed to assess whether a type 1 diabetes genetic risk score (GRS) could identify monogenic autoimmune diabetes and be useful to prioritise individuals for gene discovery studies...
February 7, 2018: Diabetologia
https://www.readbyqxmd.com/read/29416786/identification-of-differentially-expressed-genes-in-human-breast-cancer-cells-induced-by-4-hydroxyltamoxifen-and-elucidation-of-their-pathophysiological-relevance-and-mechanisms
#17
Qi Fang, Shuang Yao, Guanghua Luo, Xiaoying Zhang
While tamoxifen (TAM) is used for treating estrogen receptor (ER)a-positive breast cancer patients, its anti-breast cancer mechanisms are not completely elucidated. This study aimed to examine effects of 4-hydroxyltamoxifen (4-OH-TAM) on ER-positive (ER+) breast cancer MCF-7 cell growth and gene expression profiles. MCF-7 cell growth was inhibited by 4-OH-TAM dose-dependently with IC50 of 29 μM. 332 genes were up-regulated while 320 genes were down-regulated. The mRNA levels of up-regulated genes including STAT1, STAT2, EIF2AK2, TGM2, DDX58, PARP9, SASH1, RBL2 and USP18 as well as down-regulated genes including CCDN1, S100A9, S100A8, ANXA1 and PGR were confirmed by quantitative real-time PCR (qRT-PCR)...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29415882/swiprosin-1-deficiency-impairs-macrophage-immune-response-of-septic-mice
#18
Su Zhang, Ye Tu, Yi-Ming Sun, Ya Li, Rong-Mei Wang, Yongbing Cao, Ling Li, Li-Chao Zhang, Zhi-Bin Wang
Despite the fact that many therapeutic strategies have been adopted to delay the development of sepsis, sepsis remains one of the leading causes of death in noncoronary intensive care units. Recently, sepsis-3 was defined as life-threatening organ dysfunction due to a dysregulated host response to infection. Here, we report that swiprosin-1 (also known as EFhd2) plays an important role in the macrophage immune response to LPS-induced or cecal ligation and puncture-induced (CLP-induced) sepsis in mice. Swiprosin-1 depletion causes higher mortality, more severe organ dysfunction, restrained macrophage recruitment in the lung and kidney, and attenuated inflammatory cytokine production (including IL-1β, IL-6, TNF-α, IL-10, and IFN-γ)...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29402391/ifn-%C3%AE-and-tumor-gangliosides-implications-for-the-tumor-microenvironment
#19
Barbara Dillinger, Sarah Ahmadi-Erber, Manuel Lau, Markus A Hoelzl, Friedrich Erhart, Birgit Juergens, Dietmar Fuchs, Andreas Heitger, Stephan Ladisch, Alexander M Dohnal
Gangliosides shed by tumors into their microenvironment (TME) are immunoinhibitory. Interferon-γ (IFN-γ) may boost antitumor immune responses. Thus we wondered whether IFN-γ would counteract tumor ganglioside-mediated immune suppression. To test this hypothesis, we exposed human monocyte-derived LPS-activated dendritic cells (DC) to IFN-γ and to a highly purified ganglioside, GD1a. DC ganglioside exposure decreased TLR-dependent p38 signaling, explaining the previously observed ganglioside-induced down-modulation of pro-inflammatory surface markers and cytokines...
February 2, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29394132/decrease-in-invasion-of-htr-8-svneo-trophoblastic-cells-by-interferon-gamma-involves-cross-communication-of-stat1-and-batf2-that-regulates-the-expression-of-jun
#20
Sonam Verma, Rahul Pal, Satish Kumar Gupta
Trophoblast invasion is one of the critical steps during embryo implantation. IFNG secreted during pregnancy by uterine NK cells acts as a negative regulator of invasion. IFNG in a dose dependent fashion inhibits invasion of HTR-8/SVneo trophoblastic cells. It phosphorylates STAT1 both at tyr 701 and ser 727 residues. Silencing of STAT1 significantly increases invasion (∼59%) of the cells. Based on NGS data, out of 207 genes, BATF2 expression was significantly increased after IFNG treatment. Silencing of BATF2 significantly increases the invasion of cells with (∼53%) or without (∼44%) treatment with IFNG...
February 2, 2018: Cell Adhesion & Migration
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