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Yea-Chen Liu, Yu-Ying Hsiao, Kuo-Lung Ku, Hui-Fen Liao, Wei-Chun Chao
Macrophages play an indispensable role in the host immune defense. Macrophages can undergo polarization into classically (M1) and alternatively (M2) activated macrophages. M1 macrophages activate immune and inflammatory response, while M2 macrophages are involved in tissue remodeling. Mahonia oiwakensis (Mo) is a herbal medicine in Asia used for its anti-inflammatory and analgesic properties; however, the mechanism is unclear. This study analyzed the effect of Mo extracts and its effects on the polarization of both macrophage RAW264...
April 13, 2018: Journal of Medicinal Food
Shuxin Chen, Zepeng Du, Bingli Wu, Huiyang Shen, Chunpeng Liu, Xueli Qiu, Yufeng Zhang, Liyan Xu, Enmin Li, Zhigang Zhong
Background: In our previous study, mouse double minute 2 homolog (MDM2), insulin-like growth factor 1 (IGF1), signal transducer and activator of transcription 1 (STAT1), and Rac family small GTPase 1 (RAC1) were correlated with the recurrence of giant cell tumor of bone (GCT). The aim of this study is to use a large cohort study to confirm the involvement of these four genes in GCT recurrence. Methods: The expression of these four genes was detected and compared between GCT patients with or without recurrence...
2018: Journal of Immunology Research
Jeffrey M Riggs, Richard N Hanna, Bhargavi Rajan, Kamelia Zerrouki, Jodi L Karnell, Divya Sagar, Inna Vainshtein, Erika Farmer, Kimberly Rosenthal, Chris Morehouse, Melissa de Los Reyes, Kevin Schifferli, Meina Liang, Miguel A Sanjuan, Gary P Sims, Roland Kolbeck
Objective: We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE. Methods: IFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element-luciferase reporter cell assays and type I IFN gene signature induction...
2018: Lupus Science & Medicine
Wenxia Bai, Shudong Wang, Shanshan An, Mengjie Guo, Guangming Gong, Wenya Liu, Shaoxin Ma, Xin Li, Jihua Fu, Wenbing Yao
This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs...
March 20, 2018: Oncotarget
Shi-Mei Qi, Qiang Li, Qi Jiang, Zhi-Lin Qi, Yao Zhang
OBJECTIVE: To investigate the mechanism of chrysin in regulating lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. METHODS: RAW264.7 cells were treated with different concentrations (0, 5, 10, 20, 40, 60, 80, 100, 150, and 200 µg/mL) of chrysin for 24 h, and the cell viability was measured using CCK-8. RAW264.7 cells were pre-treated with 10, 30, or 60 µg/mL chrysin for 2 h before stimulation with LPS for different times. The levels of TNF-α, IL-6 and MCP-1 were detected by ELISA, and Western blotting was used to detect the phosphorylation of JAK- 1, JAK-2, STAT-1 and STAT-3...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Masanori Yoshizumi, Jing Zhao, Yoji Kyotani
Acute aortic dissection is the most common life-threatening vascular disease, with sudden onset of severe pain and a high fatality rate. The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to cyclic mechanical stretch (CMS), which evokes VSMC death, phenotypic switching, and migration, leading to aortic dissection. We have revealed that CMS of rat aortic smooth muscle cells (RASMCs) caused JNK- and p38-dependent cell death and that a calcium channel blocker, azelnidipine and an angiotensin II receptor antagonist, olmesartan decreased the phosphorylation of JNK and p38 and, subsequently, decreased cell death by CMS...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
C Loch, J-D Haeger, C Pfarrer
INTRODUCTION: IFNτ is the ruminant pregnancy recognition signal. In the study we investigated the autocrine influence of IFNτ on bovine F3 trophoblast cells. In detail chemotaxis, motility, metabolism, cell polarisation (CK18; ezrin) and the underlying classical (STAT1) and non-classical (MAPK42/44) signaling pathways were examined. METHODS: Cellular signaling was analysed by densitometric Western blot (STAT1, MAPK42/44, proteinkinase B) and RT-PCR (IFNAR1, -2)...
April 2018: Placenta
Marco Fiorillo, Maria Peiris-Pagès, Rosa Sanchez-Alvarez, Lucia Bartella, Leonardo Di Donna, Vincenza Dolce, Giovanni Sindona, Federica Sotgia, Anna Rita Cappello, Michael P Lisanti
Here, we show that a 2:1 mixture of Brutieridin and Melitidin, termed "BMF", has a statin-like properties, which blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl-CoA-reductase). Moreover, our results indicate that BMF functionally inhibits several key characteristics of CSCs. More specifically, BMF effectively i) reduced ALDH activity, ii) blocked mammosphere formation and iii) inhibited the activation of CSC-associated signalling pathways (STAT1/3, Notch and Wnt/beta-catenin) targeting Rho-GDI-signalling...
April 4, 2018: Biochimica et Biophysica Acta
Andrew N Wilkinson, Kate H Gartlan, Greg Kelly, Luke D Samson, Stuart D Olver, Judy Avery, Nienke Zomerdijk, Siok-Keen Tey, Jason S Lee, Slavica Vuckovic, Geoffrey R Hill
IL-6 mediates broad physiological and pathological effects through its receptor signal transducing unit gp130. Due to the reportedly wide cellular expression of gp130, IL-6 is thought to signal ubiquitously via gp130 complex formation with membrane-bound IL-6Rα or soluble IL-6Rα. gp130 signaling primarily induces p-STAT3 and p-STAT1. In contrast to the previous dogma, we show in this article that circulating mouse and human granulocytes are unable to induce p-STAT3 or p-STAT1 after stimulation with IL-6 or an IL-6/soluble IL-6R complex...
April 6, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiaochun Wang, David Goldstein, Philip J Crowe, Jia-Lin Yang
The 5-year survival rate for metastatic sarcoma is 16%. Although the phosphorylated human epidermal growth factor receptor (pEGFR/HER1) has been shown to be an independent predictor of overall survival in patients with sarcoma, we have previously demonstrated that sarcoma cell lines exhibit resistance, despite gefitinib blocking p-EGFR and signal transducers in EGFR downstream pathways. Gefitinib failed to decrease the ratio of phosphorylated (p-)signal transducer and activator of transcription (STAT3)/p-STAT1, suggesting that relative STAT3 abundance and activation may be involved in drug resistance...
March 27, 2018: International Journal of Oncology
Jianmin Zhu, Jin-Qing Liu, Min Shi, Xinhua Cheng, Miao Ding, Jianchao C Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Lanchun Lu, Xueliang Pan, Pan Zheng, Yang Liu, Xue-Feng Bai
Tumor-induced expansion of Tregs is a significant obstacle to cancer immunotherapy. However, traditional approaches to deplete Tregs are often inefficient, provoking autoimmunity. We show here that administration of IL-27-expressing recombinant adeno-associated virus (AAV-IL-27) significantly inhibits tumor growth and enhances T cell responses in tumors. Strikingly, we found that AAV-IL-27 treatment causes rapid depletion of Tregs in peripheral blood, lymphoid organs, and - most pronouncedly - tumor microenvironment...
April 5, 2018: JCI Insight
Tsukasa Nabekura, Zhiying Chen, Casey Schroeder, Taeju Park, Eric Vivier, Lewis L Lanier, Dongfang Liu
Natural killer cells are critical in the immune response to infection and malignancy. Prior studies have demonstrated that Crk family proteins can influence cell apoptosis, proliferation, and cell transformation. In this study, we investigated the role of Crk family proteins in mouse NK cell differentiation and host defense using a mouse CMV infection model. The number of NK cells, maturational state, and the majority of the NKR repertoire was similar in Crk x Crk-like (CrkL)-double-deficient and wild type NK cells...
April 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Encheng Bai, Lehe Yang, Youqun Xiang, Wanle Hu, Caleb Li, Jiayuh Lin, Xuanxuan Dai, Guang Liang, Rong Jin, Chengguang Zhao
Background: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. The poor prognosis of this disease highlights the urgent need to develop more effective therapies. Activation of the STAT3 represents a potential drug target for pancreatic cancer therapy. Currently, clinically available small-molecule inhibitors targeting STAT3 are lacking. Methods: Through bioassay screening and molecular docking, we identified a small molecule L61H46 that can potently target constitutive STAT3 signaling and kill human pancreatic cancer cells in vitro and in vivo...
2018: Cancer Management and Research
Richard Davies, Daniel Hammenfors, Brith Bergum, Petra Vogelsang, Sonia Gavasso, Johan G Brun, Roland Jonsson, Silke Appel
Primary Sjögren's syndrome (pSS) is a complex systemic autoimmune disease with heterogeneous disease manifestations. Genetic predisposition, hormonal and environmental factors are all thought to contribute to disease etiology and pathogenesis. A better understanding of the disease pathogenesis is required in order to establish new targeted therapies. We analysed MAPK/ERK and JAK/STAT signalling networks in peripheral blood mononuclear cells (PBMCs) upon stimulation with interferon alpha 2b (IFNα2b) by flow cytometry to define potentially dysfunctional intracellular signalling pathways involved in disease pathogenesis...
March 31, 2018: European Journal of Immunology
Surinder M Soond, Paul A Townsend, Sean P Barry, Richard A Knight, David S Latchman, Anastasis Stephanou
No abstract text is available yet for this article.
March 30, 2018: Journal of Biological Chemistry
Daisuke Shibahara, Kentaro Tanaka, Eiji Iwama, Naoki Kubo, Keiichi Ota, Koichi Azuma, Taishi Harada, Jiro Fujita, Yoichi Nakanishi, Isamu Okamoto
INTRODUCTION: The interaction of programmed cell death-ligand 2 (PD-L2) with programmed cell death-1 (PD-1) is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in non-small cell lung cancer (NSCLC). METHODS: PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry...
March 26, 2018: Journal of Thoracic Oncology
Ting Xi, Guizhi Zhang
BACKGROUND: Tumor differentiation is an important process in the development of cancer. It is valuable to identify key differentiation related genes in the prognosis and therapy of pancreatic adenocarcinoma. METHODS: The mRNA expression data were downloaded from the Cancer Genome Atlas database. Then, differentially expressed tumor differentiation related genes were identified. Additionally, Gene Ontology functional categories and Kyoto Encyclopedia of Genes and Genomes biochemical pathway was used to explore the function...
2018: PloS One
Zhe Zhang, Lihua Shi, Li Song, Kelly Maurer, Michele A Petri, Kathleen E Sullivan
This study was designed to define gene expression and H3K4me3 histone modifications in T cells, B cells, and monocytes in systemic lupus erythematosus (SLE). Array studies of total peripheral blood mononuclear cells have demonstrated gene expression signatures related to neutrophils, interferon, and other inflammatory pathways. It is not clear how consistent these effects are across different cell types. In this study, RNA-seq and chromatin immunoprecipitation-seq were utilized to identify gene expression patterns and H3K4me3 histone modifications related to promoter activation in SLE...
2018: Frontiers in Immunology
Shixuan Wang, Aimin Liu, Guangyu Wu, Han-Fei Ding, Shuang Huang, Stanley Nahman, Zheng Dong
Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein. Although roles for Intu have been reported during embryonic development and in the context of developmental disorders, its function and regulation in adult tissues remain poorly understood. Here we show that ablation of Intu specifically in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and leads to defective post-injury ciliogenesis. We identify signal transducer and activator of transcription 1 (STAT1) as a novel interacting partner of Intu...
March 26, 2018: Nature Communications
Siobhan Gargan, Suaad Ahmed, Rebecca Mahony, Ciaran Bannan, Silvia Napoletano, Cliona O'Farrelly, Persephone Borrow, Colm Bergin, Nigel J Stevenson
Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner...
March 9, 2018: EBioMedicine
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