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https://www.readbyqxmd.com/read/29150704/evaluation-of-immune-mediated-idiosyncratic-drug-toxicity-using-chimeric-hla-transgenic-mice
#1
Takeshi Susukida, Shigeki Aoki, Kotaro Kogo, Sota Fujimori, Binbin Song, Cong Liu, Shuichi Sekine, Kousei Ito
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT...
November 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29150604/transcriptional-signature-of-human-pro-inflammatory-th17-cells-identifies-reduced-il10-gene-expression-in-multiple-sclerosis
#2
Dan Hu, Samuele Notarbartolo, Tom Croonenborghs, Bonny Patel, Ron Cialic, Tun-Hsiang Yang, Dominik Aschenbrenner, Karin M Andersson, Marco Gattorno, Minh Pham, Pia Kivisakk, Isabelle V Pierre, Youjin Lee, Karun Kiani, Maria Bokarewa, Emily Tjon, Nathalie Pochet, Federica Sallusto, Vijay K Kuchroo, Howard L Weiner
We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ(+)IL-17(+) (TH1/17) and IFN-γ(-)IL-17(+) (TH17) CD4(+) T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150567/amplifying-ifn-%C3%AE-signaling-in-dendritic-cells-by-cd11c-specific-loss-of-socs1-increases-innate-immunity-to-infection-while-decreasing-adaptive-immunity
#3
Alejandro F Alice, Gwen Kramer, Shelly Bambina, Jason R Baird, Keith S Bahjat, Michael J Gough, Marka R Crittenden
Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-γ-polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator of TLR and cytokine receptor signaling via degradation of the receptor-signaling complex...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150440/license-to-kill-ifn-%C3%AE-regulates-antifungal-activity-of-neutrophils
#4
REVIEW
Daniel Schnepf, Peter Staeheli
Interferon-λ mediates antifungal immunity by stimulating neutrophils to generate reactive oxygen species.
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29150432/the-ikk-related-kinase-tbk1-activates-mtorc1-directly-in-response-to-growth-factors-and-innate-immune-agonists
#5
Cagri Bodur, Dubek Kazyken, Kezhen Huang, Bilgen Ekim Ustunel, Kate A Siroky, Aaron Seth Tooley, Ian E Gonzalez, Daniel H Foley, Hugo A Acosta-Jaquez, Tammy M Barnes, Gabrielle K Steinl, Kae-Won Cho, Carey N Lumeng, Steven M Riddle, Martin G Myers, Diane C Fingar
The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#6
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29149822/olive-leaf-extracts-act-as-modulators-of-the-human-immune-response
#7
Thea Magrone, Anna Spagnoletta, Rosaria Salvatore, Manrico Magrone, Francesco Dentamaro, Matteo Antonio Russo, Graziana Difonzo, Carmine Summo, Francesco Caponio, Emilio Jirillo
BACKGROUND: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs. METHODS: Peripheral blood mononuclear cells (PBMCs) from twenty-five healthy donors were cultured in the presence of 3 μg of two OLE extracts, extract A (resuspended in water) and extract B (resuspended in 70% ethanol)...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29149434/enhancement-of-therapeutic-dna-vaccine-potency-by-melatonin-through-inhibiting-vegf-expression-and-induction-of-antitumor-immunity-mediated-by-cd8-t-cells
#8
Sanaz Baghban Rahimi, Alireza Mohebbi, Gelareh Vakilzadeh, Peyvand Biglari, Soodeh Razeghi Jahromi, Seyed Reza Mohebi, Sadegh Shirian, Ali Gorji, Amir Ghaemi
To be effective, therapeutic cancer vaccines should stimulate both an effective cell-mediated and a robust cytotoxic CD8+ T-cell response against human papillomavirus (HPV)-infected cells to treat the pre-existing tumors and prevent potential future tumors. In this study, the therapeutic experiments were designed in order to evaluate antitumor effect against the syngeneic TC-1 tumor model. The anti-tumor efficacy of a HPV-16 E7 DNA vaccine adjuvanted with melatonin (MLT) was evaluated in a C57BL/6 mouse tumor model by measuring tumor growth post vaccination and the survival rate of tumor-bearing mice, analyzing the specific lymphocyte proliferation responses in control and vaccinated mice by MTT assay...
November 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29149056/characterization-of-ovine-a3z1-restriction-properties-against-small-ruminant-lentiviruses-srlvs
#9
Lorena de Pablo-Maiso, Idoia Glaria, Helena Crespo, Estanislao Nistal-Villán, Valgerdur Andrésdóttir, Damián de Andrés, Beatriz Amorena, Ramsés Reina
Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29149046/impact-of-a-single-oral-acute-dose-of-aflatoxin-b%C3%A2-on-liver-function-cytokines-and-the-lymphoproliferative-response-in-c57bl-6-mice
#10
Angélica Tieme Ishikawa, Elisa Yoko Hirooka, Paula Leonello Alvares E Silva, Ana Paula Frederico Rodrigues Loureiro Bracarense, Karina Keller Marques da Costa Flaiban, Claudia Yuri Akagi, Osamu Kawamura, Marcio Carvalho da Costa, Eiko Nakagawa Itano
Aflatoxin B₁ (AFB₁), a mycotoxin found in food and feed, exerts harmful effects on humans and animals. The liver is the earliest target of AFB₁, and its effects have been evaluated in animal models exposed to acute or chronic doses. Considering the possibility of sporadic ingestion of AFB₁-contaminated food, this study investigated the impact of a single oral dose of AFB₁ on liver function/cytokines and the lymphoproliferative response in mice. C57BL/6 mice were treated with a single oral AFB₁ dose (44, 442 or 663 μg AFB₁/kg of body weight) on the first day...
November 17, 2017: Toxins
https://www.readbyqxmd.com/read/29148853/multi-stage-subunit-vaccines-against-mycobacterium-tuberculosis-an-alternative-to-the-bcg-vaccine-or-a-bcg-prime-boost
#11
Farzad Khademi, Mohammad Derakhshan, Arshid Yousefi-Avarvand, Mohsen Tafaghodi, Saman Soleimanpour
More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants...
November 17, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/29147974/genotype-related-variations-in-proinflammatory-and-regulatory-cytokine-levels-in-treated-and-treatment-naive-hcv-infected-patients
#12
Rasoul Baharlou, Bizhan Romani, Seyed Jalal Kiani, Kaveh Sadeghi, Enayatollah Shadmand, Hadi Fazel, Farid Azizi Jalilian, Ebrahim Kord, Sajad Yaghoubi, Yousef Nikmanesh, Abbas Ahmadi Vasmehjani
Hepatitis C virus (HCV) modulates immune-related inflammatory responses to induce milder reactions leading to virus persistence. In this regard, the present study aimed to investigate the link between the HCV genotypes and the proinflammatory and regulatory cytokine levels. Ninety patients with hepatitis C infection (68 treatment-naive and 22 treated patients) and 76 healthy blood donors were studied. The serum levels of IFN-γ, IL-10, IL-17A, and IL-21 were measured by ELISA in the patients and healthy controls...
November 17, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/29147873/comparison-of-the-adjuvanticity-of-two-adjuvant-formulations-containing-de-o-acylated-lipooligosaccharide-on-japanese-encephalitis-vaccine-in-mice
#13
Ara Ko, Seo Ri Wui, Ji In Ryu, Hien Thi Thu Do, Yeon Jeong Lee, Soo Jeong Lim, Inmoo Rhee, Dae Im Jung, Jin-Ah Park, Jung-Ah Choi, Man Ki Song, Na Gyong Lee
Adjuvants are essential vaccine components used to enhance, accelerate, and/or prolong adaptive immunity against specific vaccine antigens. In this study, we compared the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS), a toll-like receptor 4 agonist, on the Japanese encephalitis (JE) vaccine in mice. Mice were immunized once or twice at a two-week interval with inactivated JE vaccine in the absence or presence of adjuvant. We found that both the alum- and the liposome-based formulation induced significantly faster and higher serum IgG antibody responses as compared with the non-adjuvanted vaccine after either one or two immunizations...
November 17, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29147626/functional-t-cells-targeting-tumor-associated-antigens-are-predictive-for-recurrence-free-survival-of-patients-with-radically-operated-non-small-cell-lung-cancer
#14
Seyer Safi, Yoshikane Yamauchi, Anchana Rathinasamy, Slava Stamova, Martin Eichhorn, Arne Warth, Geraldine Rauch, Hendrik Dienemann, Hans Hoffmann, Philipp Beckhove
In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#15
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147487/a-study-on-the-immune-response-induced-by-a-dna-vaccine-encoding-mtb32c-hbha-antigen-of-mycobacterium-tuberculosis
#16
Roghayeh Teimourpour, Hadi Peeridogaheh, Amir Teimourpour, Mohsen Arzanlou, Zahra Meshkat
Objectives: Tuberculosis (TB) has still remained a global health issue. One third of the world's population is infected with tuberculosis and the current BCG vaccine has low efficiency; hence, it is necessary to develop a new vaccine against TB. The aim of the current study was to evaluate the efficiency of a novel DNA vaccine encoding Mtb32C-HBHA antigen in inducing specific immune responses against Mycobacterium tuberculosis. Materials and Methods: A DNA plasmid vaccine expressing Mtb32C-HBHA fusion protein was constructed and its ability in protein expression was examined by RT-PCR and Western blot methods...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29147443/4-nitroquinoline-1-oxide-induced-tongue-and-esophagus-carcinogenesis-in-obese-and-diabetic-tsod-mice
#17
Takuji Tanaka, Kunihiro Kawabata, Shigeyuki Sugie
Background: Obesity and diabetes mellitus are associated with lifestyle-related carcinogenesis. They are also risk factors of esophageal adenocarcinoma, but there are only a few reports on association between obesity/diabetes and development of squamous cell carcinoma in the oral cavity and esophagus. In this study, we therefore aimed to determine whether obesity and diabetes affect oral and esophageal carcinogenesis using model mice of obesity and diabetes, the Tsumura Suzuki obese diabetes (TSOD) and Tsumura Suzuki non-obesity (TSNO) control mice, which were treated with 4-nitroquinoline 1-oxide (4-NQO) to produce tongue and esophageal carcinomas...
August 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29146976/association-of-a-variant-in-the-gene-encoding-for-erv1-chemr23-with-reduced-inflammation-in-visceral-adipose-tissue-from-morbidly-obese-individuals
#18
Cristina López-Vicario, Bibiana Rius, José Alcaraz-Quiles, Ana González-Périz, Ana Isabel Martínez-Puchol, Mireia Casulleras, Marta Duran-Güell, Ainitze Ibarzabal, Ricard Corcelles, Andrés Laguna-Fernández, Magnus Back, Esther Titos, Joan Clària
Obesity comorbidities are closely associated with chronic low-grade adipose tissue inflammation. A number of SNPs associated with inflammation has been identified, underscoring the impact of genetic determinants on this process. Here, we screened SNPs in genes with pro-inflammatory (IL-1β, IL-6, STAT3 and JAK2), anti-inflammatory (IL-10 and SOCS3) and pro-resolving (ERV1/ChemR23) properties in 101 obese and 99 non-obese individuals. Among the SNPs analyzed, we identified that individuals carrying a C allele in the rs1878022 polymorphism of the ERV1/ChemR23 gene, which encodes for the receptor of the pro-resolving mediator RvE1, had increased ERV1/ChemR23 protein expression and reduced levels of the inflammatory cytokine IL-6 in adipose tissue...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146495/polysaccharides-from-citrus-grandis-l-osbeck-suppress-inflammation-and-relieve-chronic-pharyngitis
#19
Liyan Chen, Yongfeng Lai, Lei Dong, Shasha Kang, Xiumei Chen
Chronic pharyngitis, a common inflammation of the pharyngeal mucosa, is often caused by bacteria, viruses, alcohol abuse, overuse of the voice and cigarettes. This study aimed to explore the effects of polysaccharides of Citrus grandis L. Osbeck (PCG) in relieving chronic pharyngitis and illustrate the underlying mechanisms. Polysaccharides were obtained from PCG by column chromatographic extraction. Six clinical symptom scores, such as the severity of itchy throat, hoarseness, pain, odynophagia, cough and otalgia were evaluated in chronic pharyngitis patients after the oral intake of PCG...
November 13, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29146246/nanoparticle-formulation-improves-doxorubicin-efficacy-by-enhancing-host-antitumor-immunity
#20
Eric M Mastria, Leon Y Cai, Matthew J Kan, Xinghai Li, Jeffrey L Schaal, Steven Fiering, Michael D Gunn, Mark W Dewhirst, Smita K Nair, Ashutosh Chilkoti
Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it has become recognized that doxorubicin can contribute to re-establishing host antitumor immunity through the generation of immunogenic cell death. However, the potential for delivery strategies to further enhance the immunological effects of doxorubicin has not been adequately examined...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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