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T cell inhibitory pathway

J L de Deus, A L A Dagostin, W A Varanda
Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Ming Ma, Xingxiao Yang, Lianmei Zhao, Xuexiao Wang, Lihua Liu, Wenjing Jiao, Yuanyuan Wei, Baoen Shan
Celecoxib is a newly-identified nonsteroidal anti-inflammatory drug, which has been used to treat fever in clinical practice. Celecoxib has been demonstrated to suppress the viability of various human tumor cells. However, the effect of celecoxib on response of T-cell lymphoma to chemotherapy agents remains unclear. The aim of the present study was to investigate the effect of celecoxib on chemosensitivity of human T-cell lymphoma, and to address the underlying mechanism of action. The cytotoxicity of CDDP, epirubicin and VCR on Jurkat and Hut-78 cells treated with celecoxib was assessed by MTT assay, and the half-maximal inhibitory concentration (IC50 ) value was calculated by Origin 75 software...
April 2018: Oncology Letters
Carole Sourbier, Pei-Jyun Liao, Christopher J Ricketts, Darmood Wei, Youfeng Yang, Sarah M Baranes, Benjamin K Gibbs, Lernik Ohanjanian, L Spencer Krane, Bradley T Scroggins, J Keith Killian, Ming-Hui Wei, Toshiki Kijima, Paul S Meltzer, Deborah E Citrin, Len Neckers, Cathy D Vocke, W Marston Linehan
Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15-20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation...
February 13, 2018: Oncotarget
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
Mlatovi Dégbé, Françoise Debierre-Grockiego, Amivi Tété-Bénissan, Héloïse Débare, Kodjo Aklikokou, Isabelle Dimier-Poisson, Messanvi Gbeassor
Tectona grandis (teak) and Vernonia amygdalina (bitter leaf) are plants used in traditional medicine in West Africa. In this study, we tested ethanolic and hydro-ethanolic extracts of bark and leaves of T. grandis and ethanolic extract of leaves of V. amygdalina for their inhibitory effect on Toxoplasma gondii, a protozoan parasite responsible for toxoplasmosis. Ethanolic extract of V. amygdalina leaves had proportional contents of phenols, tannins, flavonoids, and polysaccharides. This extract presented the highest efficacy against T...
2018: Parasite: Journal de la Société Française de Parasitologie
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
Claudia Fumarola, Pier Giorgio Petronini, Roberta Alfieri
Cell metabolic reprogramming is one of the main hallmarks of cancer and many oncogenic pathways that drive the cancer-promoting signals also drive the altered metabolism. This review focuses on recent data on the use of oncogene-targeting agents as potential modulators of deregulated metabolism in different solid cancers. Many drugs, originally designed to inhibit a specific target, then have turned out to have different effects involving also cell metabolism, which may contribute to the mechanisms underlying the growth inhibitory activity of these drugs...
March 9, 2018: Biochemical Pharmacology
Rebeca Hid Cadena, Wayel H Abdulahad, G A P Hospers, T T Wind, Annemieke M H Boots, Peter Heeringa, Elisabeth Brouwer
Age-associated changes in the immune system including alterations in surface protein expression are thought to contribute to an increased susceptibility for autoimmune diseases. The balance between the expression of coinhibitory and costimulatory surface protein molecules, also known as immune checkpoint molecules, is crucial in fine-tuning the immune response and preventing autoimmunity. The activation of specific inhibitory signaling pathways allows cancer cells to evade recognition and destruction by the host immune system...
2018: Frontiers in Immunology
Yi Gao, Jianjian Yang, Yixin Cai, Shengling Fu, Ni Zhang, Xiangning Fu, Lequn Li
IFN-γ plays a crucial role in anti-tumor responses but also induces expression of PD-L1, a well-established inhibitor of anti-tumor immune function. Understanding how molecular signaling regulates the function of IFN-γ might improve its anti-tumor efficacy. Here we show that the tumor expression of IFN-γ expression alone has no significant prognostic value in patients with locally advanced lung adenocarcinoma. Surprisingly, patients with tumors expressing both IFN-γ and PD-L1 have the best prognosis compared to those with tumors expressing IFN-γ or PD-L1 alone...
March 8, 2018: International Journal of Cancer. Journal International du Cancer
Xiaoling Xie, Weijun Zhou, Yuxing Hu, Yiran Chen, Honghao Zhang, Yuhua Li
The identification and characterization of tumor-associated antigens (TAAs) that generate specific cytotoxic T lymphocytes (CTLs) are vital to the development of cancer immunotherapy. The epidermal growth factor receptor (EGFR) pathway substrate 8 gene (Eps8) is involved in regulating cancer progression and might be an ideal antigen. In this study, we searched for novel human leukocyte antigen (HLA)-A*2402-restricted epitopes derived from the Eps8 protein via the HLA-binding prediction algorithm. Among four candidates, peptides 327 (EFLDCFQKF), 534 (KYAKSKYDF) and 755 (LFSLNKDEL) induced peptide-specific CTLs to secrete higher levels of interferon-gamma (IFN-γ) and showed enhanced cytotoxic activity against malignant cancer cells...
March 7, 2018: Cell Death & Disease
F F Wang, Y Wang, L Wang, T S Wang, Y P Bai
BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled...
March 7, 2018: Clinical and Experimental Dermatology
T-J Liu, J-L Guo, H-K Wang, X Xu
OBJECTIVE: Oral tongue squamous cell carcinoma (OTSCC) is the most frequently encountered malignant epithelial tumors. Semaphorin-7A is a membrane-associated/secreted protein that plays an essential role in the migration and progression of human malignancies. We aimed to investigate the mechanisms of Semaphorin-7A in the growth and migration of OTSCC. MATERIALS AND METHODS: The expressions of Semaphorin-7A in cells were tested by RT-PCR, Western blot, and Immunofluorescence, separately...
February 2018: European Review for Medical and Pharmacological Sciences
Matías A Medina, Víctor M Andrade, Mario O Caracci, Miguel E Avila, Daniela A Verdugo, Macarena F Vargas, Giorgia D Ugarte, Ariel E Reyes, Carlos Opazo, Giancarlo V De Ferrari
Synaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays...
March 5, 2018: Translational Psychiatry
Po-Yuan Shih, Shu-Jen Chou, Caroline Müller, Barbara Ann Halkier, Rosalia Deeken, Erh-Min Lai
Agrobacterium tumefaciens is the causal agent of crown gall disease in a wide range of plants via a unique interkingdom DNA transfer from bacterial cells into the plant genome. A. tumefaciens is capable of transferring its T-DNA into different plant parts at different developmental stages for transient and stable transformation. However, the plant genes and mechanisms involved in these transformation processes are not well understood. We used Arabidopsis thaliana Col-0 seedlings to reveal the gene expression profiles at early time points during Agrobacterium infection...
March 2, 2018: Molecular Plant Pathology
Sohrab Asefi, Massoud Seifi, Ghazal Hatami Fard, Ali Lotfi
Background: Curcumin is the most active compound in turmeric. It can suppress the nuclear factor kappa-light-chain-enhancer of activated B cells pathway and prevent the osteoclastogenesis procedure. This study aimed to be the first to evaluate the effect of curcumin on the rate of orthodontic tooth movement (OTM). Materials and Methods: Forty rats were used as follows in each group: (1) negative control: Did not receive any appliance or injection; (2) positive control: received 0...
January 2018: Dental Research Journal
Yanxia Guo, Alice M Walsh, Mary Canavan, Mihir D Wechalekar, Suzanne Cole, Xuefeng Yin, Brittney Scott, Mathew Loza, Carl Orr, Trudy McGarry, Michele Bombardieri, Frances Humby, Susanna M Proudman, Costantino Pitzalis, Malcolm D Smith, Joshua R Friedman, Ian Anderson, Loui Madakamutil, Douglas J Veale, Ursula Fearon, Sunil Nagpal
Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development...
2018: PloS One
Bethtrice Elliott, DeAdra L Zackery, Vanessa A Eaton, Re'Josef T Jones, Fisseha Abebe, Camille C Ragin, Shafiq A Khan
Epidemiological studies show that the incidence and mortality rates of prostate cancer (PCa) are significantly higher in African-American (AA) men when compared to Caucasian (CA) men in the US. Transforming growth factor β (TGFβ) signaling pathway is linked to health disparities in African-Americans. Recent studies suggest a role of TGFβ3 in cancer metastases and its effect on the migratory and invasive behavior; however, its role in prostate cancer in African American men has not been studied. We determined the circulating levels of TGFβ3 in AA and CA men diagnosed with PCa using ELISA...
February 21, 2018: Carcinogenesis
Shohreh Majd, John H T Power
BACKGROUND: Emerging evidence supports the hypothesis that metabolism dysfunction is involved in pathogenesis of Alzheimer's disease (AD). One aspect of metabolic dysfunction includes dysregulation of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) metabolic axis, which is extensively present in some of the leading causes of AD such as cerebrovascular diseases, type 2 diabetes and brain ischaemic events. While the molecular basis underlying this metabolic dysregulation remains a significant challenge, mitochondrial dysfunction due to aging appears to be an essential factor to activate AMPK/mTOR signaling pathway, leading to abnormal neuronal energy metabolism and AD pathology...
February 22, 2018: Current Alzheimer Research
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