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https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#1
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29330473/endothelial-heparan-sulfate-deficiency-reduces-inflammation-and-fibrosis-in-murine-diabetic-nephropathy
#2
Ditmer T Talsma, Kirankumar Katta, Marieke A B Ettema, Berna Kel, Marion Kusche-Gullberg, Moh R Daha, Coen A Stegeman, Jacob van den Born, Lianchun Wang
Inflammation plays a vital role in the development of diabetic nephropathy, but the underlying regulatory mechanisms are only partially understood. Our previous studies demonstrated that, during acute inflammation, endothelial heparan sulfate (HS) contributes to the adhesion and transendothelial migration of leukocytes into perivascular tissues by direct interaction with L-selectin and the presentation of bound chemokines. In the current study, we aimed to assess the role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic nephropathy mouse model...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29330469/mycobacterium-tuberculosis-exploits-a-molecular-off-switch-of-the-immune-system-for-intracellular-survival
#3
Ulrich von Both, Maurice Berk, Paul-Michael Agapow, Joseph D Wright, Anna Git, Melissa Shea Hamilton, Greg Goldgof, Nazneen Siddiqui, Evangelos Bellos, Victoria J Wright, Lachlan J Coin, Sandra M Newton, Michael Levin
Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human macrophages by subversion of immune mechanisms. Although these immune evasion strategies are well characterised functionally, the underlying molecular mechanisms are poorly understood. Here we show that during infection of human whole blood with M. tuberculosis, host gene transcriptional suppression, rather than activation, is the predominant response. Spatial, temporal and functional characterisation of repressed genes revealed their involvement in pathogen sensing and phagocytosis, degradation within the phagolysosome and antigen processing and presentation...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327613/potential-immunotherapies-for-sarcoidosis
#4
Van Le, Elliott D Crouser
Sarcoidosis is a chronic granulomatous inflammatory disease that commonly causes lung disease, but can affect other vital organs and tissues. The cause of sarcoidosis is unknown, and current therapies are commonly limited by lack of efficacy, adverse side effects, and excessive cost. Areas covered: The manuscript will provide a review of current concepts relating to the pathogenesis of sarcoidosis, and how these disease mechanisms may be leveraged to develop more effective treatments for sarcoidosis. It provides only a brief summary of currently accepted therapy, while focusing more extensively on potential novel therapies...
January 12, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29324800/hepcidin-deficiency-and-iron-deficiency-do-not-alter-tuberculosis-susceptibility-in-a-murine-m-tb-infection-model
#5
Rachel Harrington-Kandt, Elena Stylianou, Lucy A Eddowes, Pei Jin Lim, Lisa Stockdale, Nawamin Pinpathomrat, Naomi Bull, Janet Pasricha, Marta Ulaszewska, Yulia Beglov, Sophie Vaulont, Hal Drakesmith, Helen McShane
Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection...
2018: PloS One
https://www.readbyqxmd.com/read/29321062/notch-signaling-triggered-via-the-ligand-dll4-impedes-m2-macrophage-differentiation-and-promotes-their-apoptosis
#6
Sylvain Pagie, Nathalie Gérard, Béatrice Charreau
BACKGROUND: Notch signaling controls many cellular processes, including cell fate determination, cell differentiation, proliferation and apoptosis. In mammals, four Notch receptors (Notch 1-4) can interact with five distinct ligands [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported that Notch activation is modulated in endothelial cells and monocytes during inflammation and showed that inflammation upregulates DLL4 on endothelial cells. DLL4 promotes differentiation of blood monocytes into proinflammatory M1 macrophages...
January 10, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29319347/sigma-factors-mediated-signaling-in-mycobacterium-tuberculosis
#7
Peifu Zhou, Xinpeng Wang, Yuzhong Zhao, Wei Yuan, Jianping Xie
Activation of signaling cascades is critical for Mycobacterium tuberculosis (Mtb) to adapt the macrophage lifestyle. Parallel to several signal systems, sigma factor systems, especially the extra-cytoplasmic function sigma factors, are crucial for Mtb signaling. Most sigma factors lack a signal sensory domain and often are activated by various proteins that perceive the environmental cues and relay the signals through variegated post-translational modifications via the activity of antisigma factor, protein kinase and related transcriptional regulators...
January 10, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29315766/disruption-of-adenosine-2a-receptor-exacerbates-nafld-through-increasing-inflammatory-responses-and-srebp1c-activity
#8
Yuli Cai, Honggui Li, Mengyang Liu, Ya Pei, Juan Zheng, Jing Zhou, Xianjun Luo, Wenya Huang, Linqiang Ma, Qiuhua Yang, Shaodong Guo, Xiaoqiu Xiao, Qifu Li, Tianshu Zeng, Fanyin Meng, Heather Francis, Shannon Glaser, Lulu Chen, Yuqing Huo, Gianfranco Alpini, Chaodong Wu
Adenosine 2A receptor (A2A R) exerts protective roles in endotoxin- and/or ischemia-induced tissue damages. However, the role for A2A R in non-alcoholic fatty liver disease (NAFLD) remains largely unknown. We sought to examine the effects of global and/or myeloid cell-specific A2A R disruption on the aspects of obesity-associated NAFLD and to elucidate the underlying mechanisms. Global and/or myeloid cell-specific A2A R-disrupted mice, as well as control mice were fed a high-fat diet (HFD) to induce NAFLD. Also, bone marrow-derived macrophages and primary mouse hepatocytes were examined for inflammatory and metabolic responses...
January 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29311580/lsd1-activation-promotes-inducible-emt-programs-and-modulates-the-tumour-microenvironment-in-breast-cancer
#9
T Boulding, R D McCuaig, A Tan, K Hardy, F Wu, J Dunn, M Kalimutho, C R Sutton, J K Forwood, A G Bert, G J Goodall, L Malik, D Yip, J E Dahlstrom, A Zafar, K K Khanna, S Rao
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311317/tolerogenic-nanoparticles-restore-the-antitumor-activity-of-recombinant-immunotoxins-by-mitigating-immunogenicity
#10
Ronit Mazor, Emily M King, Masanori Onda, Nicolas Cuburu, Selamawit Addissie, Devorah Crown, Xiu-Fen Liu, Takashi Kei Kishimoto, Ira Pastan
Protein-based drugs are very active in treating cancer, but their efficacy can be limited by the formation of neutralizing antidrug antibodies (ADAs). Recombinant immunotoxins are proteins that are very effective in patients with leukemia, where immunity is suppressed, but induce ADAs, which compromise their activity, in patients with intact immunity. Here we induced a specific, durable, and transferable immune tolerance to recombinant immunotoxins by combining them with nanoparticles containing rapamycin (SVP-R)...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29311239/induction-of-il-10-by-borrelia-burgdorferi-is-regulated-by-the-action-of-cd14-dependent-p38-mapk-and-camp-mediated-chromatin-remodeling
#11
Bikash Sahay, Kathleen Bashant, Nicole J Nelson, Rebeca L Patsey, Shiva Kumar Gadila, Rebecca Boohaker, Ashutosh Verma, Klemen Strle, Timothy J Sellati
Host genotype influences the severity of murine Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi C57BL/6 (B6) mice develop mild, whereas C3H/HeN (C3H) mice develop severe Lyme arthritis. Differential expression of interleukin 10 (IL-10) has long been associated with mouse strain differences in Lyme pathogenesis; however, the underlying mechanism(s) of this genotype-specific IL-10 regulation remained elusive. Herein we reveal a cAMP-mediated mechanism of IL-10 regulation in B6 macrophages that is substantially diminished in C3H macrophages...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29309928/foxos-in-cancer-immunity-knowns-and-unknowns
#12
REVIEW
Youcai Deng, Fangjie Wang, Tiffany Hughes, Jianhua Yu
In the tumor microenvironment (TME), cancer cells, stromal cells, and immune cells, along with their extracellular factors, have profound effects on either promoting or repressing anti-cancer immunity. Accumulating evidence has shown the paradoxical intrinsic role of the Forkhead box O (FOXO) family of transcription factors in cancer, which can act as a tumor repressor while also maintaining cancer stem cells. FOXOs also regulate cancer immunity. FOXOs promote antitumor activity through negatively regulating the expression of immunosuppressive proteins, such as programmed death 1 ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) in tumor cells or stromal cells, which can shape an immunotolerant state in the TME...
January 5, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29309756/dichotomous-function-of-il-33-in-health-and-disease-from-biology-to-clinical-implications
#13
REVIEW
Harald Braun, Inna S Afonina, Christina Mueller, Rudi Beyaert
Interleukin (IL)-33 is a cytokine that is released from epithelial and endothelial cells at barrier surfaces upon tissue stress or damage to operate as an alarmin. IL-33 has been primarily implicated in the induction of T helper (Th) 2 type immune responses. Therefore, IL-33 has attracted a lot of interest as a potential therapeutic target in asthma and other allergic diseases. Over the years, it has become clear that IL-33 has a much broader activity and also contributes to Th1 immunity, expanding the possibilities for therapeutic modulation of IL-33 activity to multiple inflammatory diseases...
January 5, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29308326/depletion-of-tumor-associated-macrophages-switches-the-epigenetic-profile-of-pancreatic-cancer-infiltrating-t-cells-and-restores-their-anti-tumor-phenotype
#14
Simone Borgoni, Andrea Iannello, Santina Cutrupi, Paola Allavena, Maurizio D'Incalci, Francesco Novelli, Paola Cappello
Pancreatic Ductal Adenocarcinoma (PDA) is characterized by a complex tumor microenvironment that supports its progression, aggressiveness and resistance to therapies. The delicate interplay between cancer and immune cells creates the conditions for PDA development, particularly due to the functional suppression of T cell anti-tumor effector activity. However, some of the mechanisms involved in this process are still poorly understood. In this study, we analyze whether the functional and epigenetic profile of T cells that infiltrate PDA is modulated by the microenvironment, and in particular by tumor-associated macrophages (TAMs)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308321/blocking-the-cd47-sirp%C3%AE-axis-by-delivery-of-anti-cd47-antibody-induces-antitumor-effects-in-glioma-and-glioma-stem-cells
#15
Feng Li, Bingke Lv, Yang Liu, Tian Hua, Jianbang Han, Chengmei Sun, Limin Xu, Zhongfei Zhang, Zhiming Feng, Yingqian Cai, Yuxi Zou, Yiquan Ke, Xiaodan Jiang
Tumor initiating cells or cancer stem cells (CSCs) play an important role in the initiation, development, metastasis, and recurrence of tumors. However, traditional therapies have limited effects against CSCs and targeting these cells is crucial when developing new therapeutic strategies against cancer. One potentially targetable factor is CD47, a member of the immunoglobulin superfamily. This protein acts as an anti-phagocytic "don't eat me" signal and is often found expressed by cancer cells, particularly CSCs...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29307886/adoptive-transfer-of-il-10-regulatory-b-cells-decreases-myeloid-derived-macrophages-in-the-central-nervous-system-in-a-transgenic-amyotrophic-lateral-sclerosis-model
#16
Andrea Pennati, Seneshaw Asress, Jonathan D Glass, Jacques Galipeau
No abstract text is available yet for this article.
January 8, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29306008/the-mals-5-utr-weakens-the-ability-of-salmonella-enterica-serovar-typhi-to-survive-in-macrophages-by-increasing-intracellular-atp-levels
#17
Fang Dong, Lin Xia, Renfei Lu, Xin Zhao, Yiquan Zhang, Ying Zhang, Xinxiang Huang
Bacterial non-coding RNAs (ncRNAs), as important regulatory factors, are involved in many cellular processes, including virulence and protection against environmental stress. The 5' untranslated region (UTR) of malS (named malS-5'UTR), a regulatory ncRNA, increases the invasive capacity and influences histidine biosynthesis in Salmonella enterica serovar Typhi (S. Typhi). In this study, we found that overexpression of the malS-5'UTR decreased S. Typhi survival within macrophages. A microarray analysis of a strain overexpressing the malS-5'UTR revealed a significant increase in the mRNA levels of the atp operon...
January 3, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29305416/involvement-of-hepcidin-in-iron-metabolism-dysregulation-in-gaucher-disease
#18
Thibaud Lefebvre, Niloofar Reihani, Raed Daher, Thierry Billette de Villemeur, Nadia Belmatoug, Christian Rose, Yves Colin-Aronovicz, Hervé Puy, Caroline Le Van Kim, Mélanie Franco, Zoubida Karim
Gaucher disease is an inherited deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in tissues such as the spleen, liver, and bone marrow. The resulting lipid-laden macrophages lead to the appearance of Gaucher cells. Anemia associated with an unexplained hyperferritinemia is a frequent finding in Gaucher disease, but whether this pathogenesis is related to an iron metabolism disorder has remained unclear. To investigate this issue, we explored the iron status of a large cohort of 90 type I Gaucher disease patients, including 66 patients treated with enzyme replacement therapy...
January 5, 2018: Haematologica
https://www.readbyqxmd.com/read/29305330/role-of-a-macrophage-receptor-with-collagenous-structure-marco-in-regulating-monocyte-macrophage-functions-in-ayu-plecoglossus-altivelis
#19
Le Zhang, Li Nie, Shi-Yu Cai, Jie Chen, Jiong Chen
Macrophage receptor with collagenous structure (MARCO) plays essential roles in phagocytic cell-mediated innate immune responses. However, studies regarding MARCO, especially its functions, are limited in teleost species. In this study, we identified a MARCO molecule (PaMARCO) from ayu (Plecoglossus altivelis). PaMARCO shared conserved functional domains with its mammalian counterparts. Sequence analysis showed that PaMARCO was most closely related to its rainbow trout (Oncorhynchus mykiss) counterpart. PaMARCO expression was upregulated in all tested immune tissues and monocytes/macrophages (MO/MΦ) upon Vibrio anguillarum infection, and blocking its function significantly decreased the immune responses of MO/MΦ during infection...
January 2, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29305258/irf-2-haploinsufficiency-causes-enhanced-imiquimod-induced-psoriasis-like-skin-inflammation
#20
Makiko Kawaguchi, Tomonori Oka, Makoto Sugaya, Hiraku Suga, Takayuki Kimura, Sohshi Morimura, Hideki Fujita, Shinichi Sato
BACKGROUNDS: IFN regulatory factor (IRF)-2 is one of the potential susceptibility genes for psoriasis, but how this gene influences psoriasis pathogenesis is unclear. Topical application of imiquimod (IMQ), a TLR7 ligand, induces psoriasis-like skin lesions in mice. OBJECTIVE: The aim of this study was to investigate whether IRF-2 gene status would influence severity of skin disease in IMQ-treated mice. METHODS: Imiquimod-induced psoriasis-like skin inflammation was assessed by clinical findings, histology, and cytokine expression...
December 28, 2017: Journal of Dermatological Science
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