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Cytokine signaling

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https://www.readbyqxmd.com/read/28445985/interleukin-22-promotes-aerobic-glycolysis-associated-with-tumor-progression-via-targeting-hexokinase-2-in-human-colon-cancer-cells
#1
Yulin Liu, Fan Xiang, Yongming Huang, Liang Shi, Chaojie Hu, Yiming Yang, Di Wang, Nan He, Kaixiong Tao, Ke Wu, Guobin Wang
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445980/the-pp4r1-sub-unit-of-protein-phosphatase-pp4-is-essential-for-inhibition-of-nf-%C3%AE%C2%BAb-by-merkel-polyomavirus-small-tumour-antigen
#2
Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, Rachel Toth, J Simon C Arthur, Adrian Whitehouse, Andrew Macdonald
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445821/the-ampk-mtor-pathway-is-involved-in-d-dopachrome-tautomerase-gene-transcription-in-adipocytes-differentiated-from-sgbs-cells-a-human-preadipocyte-cell-line
#3
Takeo Iwata, Kyoko Kuribayashi, Masahiko Nakasono, Noriko Saito-Tarashima, Noriaki Minakawa, Noriko Mizusawa, Rie Kido, Katsuhiko Yoshimoto
In adipose tissue, D-dopachrome tautomerase (DDT), a cytokine with structural similarity to macrophage migration inhibitory factor, is mainly expressed in adipocytes rather than preadipocytes and acts as an anti-obesity adipokine in an autocrine manner. However, its transcriptional regulation is largely unknown. In order to explore molecules affecting DDT transcription, a chemical library screening using HEK293 cells stably expressing a DDT promoter-reporter construct was performed. Several derivatives of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, were identified as transcriptional activators of the DDT gene...
April 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28445727/environmental-enrichment-induces-pericyte-and-iga-dependent-wound-repair-and-lifespan-extension-in-a-colon-tumor-model
#4
Benjamin D Bice, Megan R Stephens, Stephanie J Georges, Ashlee R Venancio, Peter C Bermant, Annika V Warncke, Kajsa E Affolter, Julio R Hidalgo, Melinda L Angus-Hill
Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior, and social interactions. Using a Tcf4(Het/+)Apc(Min/+)-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4(Het/+)Apc(Min/+) males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor (NHR) signaling, both of which are common in the wound repair process...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445677/overexpression-of-the-cytokine-baff-and-autoimmunity-risk
#5
Maristella Steri, Valeria Orrù, M Laura Idda, Maristella Pitzalis, Mauro Pala, Ilenia Zara, Carlo Sidore, Valeria Faà, Matteo Floris, Manila Deiana, Isadora Asunis, Eleonora Porcu, Antonella Mulas, Maria G Piras, Monia Lobina, Sandra Lai, Mara Marongiu, Valentina Serra, Michele Marongiu, Gabriella Sole, Fabio Busonero, Andrea Maschio, Roberto Cusano, Gianmauro Cuccuru, Francesca Deidda, Fausto Poddie, Gabriele Farina, Mariano Dei, Francesca Virdis, Stefania Olla, Maria A Satta, Mario Pani, Alessandro Delitala, Eleonora Cocco, Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Paola Ferrigno, Maria Ban, Nadia Barizzone, Maurizio Leone, Franca R Guerini, Matteo Piga, Davide Firinu, Ingrid Kockum, Izaura Lima Bomfim, Tomas Olsson, Lars Alfredsson, Ana Suarez, Patricia E Carreira, Maria J Castillo-Palma, Joseph H Marcus, Mauro Congia, Andrea Angius, Maurizio Melis, Antonio Gonzalez, Marta E Alarcón Riquelme, Berta M da Silva, Maurizio Marchini, Maria G Danieli, Stefano Del Giacco, Alessandro Mathieu, Antonello Pani, Stephen B Montgomery, Giulio Rosati, Jan Hillert, Stephen Sawcer, Sandra D'Alfonso, John A Todd, John Novembre, Gonçalo R Abecasis, Michael B Whalen, Maria G Marrosu, Alessandra Meloni, Serena Sanna, Myriam Gorospe, David Schlessinger, Edoardo Fiorillo, Magdalena Zoledziewska, Francesco Cucca
Background Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Methods Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE)...
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28444871/dihydroberberine-exhibits-synergistic-effects-with-sunitinib-on-nsclc-nci-h460-cells-by-repressing-map-kinase-pathways-and-inflammatory-mediators
#6
Bingling Dai, Yujiao Ma, Wenjie Wang, Yingzhuan Zhan, Dongdong Zhang, Rui Liu, Yanmin Zhang
Highly effective and attenuated dose schedules are good regimens for drug research and development. Combination chemotherapy is a good strategy in cancer therapy. We evaluated the antitumour effects of dihydroberberine combined with sunitinib (DCS) on the human non-small cell lung cancer cell lines (NSCLC), A549, NCI-H460, and NCI-H1299 in vitro and in vivo. DCS showed synergic effects on NCI-H460 cell proliferation, colony formation and transplantable tumour growth, which suggested dihydroberberine increases the sensitivity of lung carcinoma to sunitinib...
April 26, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28444548/post-effect-of-air-quality-improvement-on-biomarkers-for-systemic-inflammation-and-microparticles-in-asthma-patients-after-the-2008-beijing-olympic-games-a-pilot-study
#7
Jinming Gao, Xiaohua Xu, Zhekang Ying, Lei Jiang, Mianhua Zhong, Aixia Wang, Lung-Chi Chen, Bo Lu, Qinghua Sun
This study's aim was to investigate the post-effect of an air quality improvement on systemic inflammation and circulating microparticles in asthmatic patients during, and 2 months after, the Beijing Olympics 2008. We measured the levels of circulating inflammatory cytokines and microparticles in the peripheral blood from asthma patients and healthy controls during (phase 1), and 2 months after (phase 2) the Beijing 2008 Olympic Games. The concentrations of circulating cytokines (including TNFα, IL-6, IL-8, and IL-10) were still seen reduced in phase 2 when compared with those in phase 1...
April 25, 2017: Inflammation
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#8
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28444170/neuronal-activity-tgf%C3%AE-signaling-and-unpredictable-chronic-stress-modulate-transcription-of-gadd45-family-members-and-dna-methylation-in-the-hippocampus
#9
Daniela Grassi, Henriette Franz, Riccardo Vezzali, Patrick Bovio, Stefanie Heidrich, Fariba Dehghanian, Natalia Lagunas, Catherine Belzung, Kerstin Krieglstein, Tanja Vogel
Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB)...
April 21, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28444107/apelin-13-inhibits-lipoprotein-lipase-expression-via-the-apj-pkc%C3%AE-mir-361-5p-signaling-pathway-in-thp-1-macrophage-derived-foam-cells
#10
Xin Zhang, Qiong Ye, Duo Gong, Yuan Lv, Haipeng Cheng, Chong Huang, Lingyan Chen, Zhenwang Zhao, Liang Li, Xie Wei, Min Zhang, Xiaodan Xia, Xiaohua Yu, Xilong Zheng, Shuzhi Wang, Zongbao Wang, Chaoke Tang
Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells...
April 21, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#11
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28443393/cd14-gene-silencing-alters-the-microrna-expression-profile-of-raw264-7-cells-stimulated-by-brucella-melitensis-infection
#12
Hui Rong, Hanwei Jiao, Yongchang Hao, Feng Pang, Guohua Li, Dongmei Peng, Yaying Li, Yuanzhi Wang, Hui Zhang, Quanshui Fan, Fengyang Wang, Chuangfu Chen, Li Du
Innate recognition of Brucella spp. is a key step in the activation of inflammation. CD14 binds PAMPs and is involved in LPS-induced pro-inflammatory cytokine release. Previously we showed that knock down of CD14 in RAW264.7 macrophages disrupted Brucella-host interactions. However, its effect on the macrophage microRNA (miRNA) expression profile, especially after stimulation by Brucella infection, is still unclear. To identify miRNAs involved in the macrophage response to Brucella infection, we performed miRNA expression profiling of CD14 knock-down RAW264...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28442634/pharmacologic-targeting-erk1-2-attenuates-the-development-and-progression-of-hyperuricemic-nephropathy-in-rats
#13
Na Liu, Liuqing Xu, Yingfeng Shi, Lu Fang, Hongwei Gu, Hongrui Wang, Xiaoqiang Ding, Shougang Zhuang
The pathogenesis of hyperuricemia-induced chronic kidney disease is largely unknown. In this study, we investigated whether extracellular signal-regulated kinases1/2 (ERK1/2) would contribute to the development of hyperuricemic nephropathy (HN). In a rat model of HN induced by feeding mixture of adenine and potassium oxonate, increased ERK1/2 phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, in parallel with diminished levels of renal function and increased urine microalbumin excretion...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442605/the-toll-like-receptor-4-antagonist-eritoran-protects-mice-from-lethal-filovirus-challenge
#14
Patrick Younan, Palaniappan Ramanathan, Jessica Graber, Fabian Gusovsky, Alexander Bukreyev
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen intermittent reemergence since it was officially declared over in February of 2016, has demonstrated the need for the rapid development of therapeutic intervention strategies. Indirect evidence has suggested that the EBOV infection shares several commonalities associated with the onset of bacterial sepsis, including the development of a "cytokine storm." Eritoran, a Toll-like receptor 4 (TLR4) antagonist, was previously shown to result in protection of mice against lethal influenza virus infection...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28442583/seletalisib-characterization-of-a-novel-potent-and-selective-inhibitor-of-pi3k%C3%AE
#15
Rodger A Allen, Daniel C Brookings, Mark J Powell, Jean Delgado, Lindsay K Shuttleworth, Mark Merriman, Ian J Fahy, Roohi Tewari, John P Silva, Louise J Healy, Gareth C G Davie, Breda Twomey, Rona M Cutler, Apoorva Kotian, Andrea Crosby, Gillian McCluskey, Gillian Watt, Andrew Payne
PI3Ks are key signaling enzymes regulating cellular survival, development and function. Expression of the PI3Kδ isoform is largely restricted to leukocytes and it plays a key role in immune cell development and function. Seletalisib is a novel small molecule inhibitor of PI3Kδ that was evaluated in biochemical assays, cellular assays of adaptive and innate immunity, and an in vivo rat model of inflammation. Our findings show that seletalisib is a potent, ATP-competitive and highly selective PI3Kδ inhibitor able to block AKT phosphorylation following activation of the BCR in a B-cell line...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28442574/the-r753q-polymorphism-in-toll-like-receptor-2-tlr2-attenuates-innate-immune-responses-to-mycobacteria-and-impairs-myd88-adapter-recruitment-to-tlr2
#16
Goutham Pattabiraman, Rahul Panchal, Andrei E Medvedev
Toll-like receptor (TLR) 2 plays a critical role in host defenses against mycobacterial infections. The Arg753Gln (R753Q) TLR2 polymorphism has been associated with increased incidence of tuberculosis and infections with non-tuberculous mycobacteria in human populations, but the mechanisms by which this polymorphism affects TLR2 signaling are unclear. In this study, we determined the impact of the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis. Upon infection with M. smegmatis, macrophages from knock-in (KI) mice harboring R753Q TLR2 expressed lower levels of TNF-α, IL-1β, IL-6 and IL-10 compared to cells from wild-type (WT) mice but both R753Q TLR2 and WT mice exhibited comparable bacterial burdens...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442557/high-phosphate-induces-a-pro-inflammatory-response-by-vascular-smooth-muscle-cells-modulation-by-vitamin-d-derivatives
#17
Julio M Martínez-Moreno, Carmen Herencia, Addy Montes de Oca, Juan M Díaz-Tocados, Noemi Vergara, Mª José Gomez, Silvia D López-Argüello, Antonio Camargo, Esther Peralbo-Santaella, Maria E Rodríguez-Ortiz, Antonio Canalejo, Mariano Rodriguez, Juan J Muñoz-Castañeda, Yolanda Yolanda Almaden
In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently correlated with inflammation, the present study aimed to investigate an independent direct effect of HP as a pro-inflammatory factor in VSMCs. A possible modulatory effect of vitamin D was also investigated. The study was performed in an in vitro model of human aortic smooth muscle cells (HASMCs). Incubation of cells in a HP (3...
April 25, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28442350/extracellular-nampt-visfatin-induces-proliferation-through-erk1-2-and-akt-and-inhibits-apoptosis-in-breast-cancer-cells
#18
Zafar Gholinejad, Nejat Kheiripour, Mitra Nourbakhsh, Davod Ilbeigi, Kiarash Behroozfar, Zahra Hesari, Abolfazl Golestani, Mohammad Shabani, Nahid Einollahi
BACKGROUND: Visfatin is a novel adipokine and proinflammatory cytokine which is implicated in breast cancer progression. The exact proliferative and anti-apoptotic mechanisms of visfatin are still under debate. In this study, the effect of extracellular visfatin on proliferation and apoptosis of breast cancer cells were investigated considering key regulatory molecules in these procedures. METHODS: BrdU (Bromodeoxyuridine) experiment was used to assess cell proliferation in response to visfatin treatment...
April 22, 2017: Peptides
https://www.readbyqxmd.com/read/28442260/synthesis-of-benzoxazole-derivatives-as-interleukin-6-antagonists
#19
Darong Kim, Hee Yeon Won, Eun Sook Hwang, Young-Kook Kim, Hea-Young Park Choo
A growing number of studies have demonstrated that interleukin (IL)-6 plays pathological roles in the development of chronic inflammatory disease and autoimmune disease by activating innate immune cells and by stimulating adaptive inflammatory T cells. So, suppression of IL-6 function may be beneficial for prevention and treatment of chronic inflammatory disease. This study reports that a series of synthetic derivatives of benzoxazole have suppressive effects on IL-6-mediated signaling. Among 16 synthetic derivatives of benzoxazole, the compounds 4, 6, 11, 15, 17, and 19 showed a strong suppressive activity against IL-6-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 by 80-90%...
April 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28441586/kobuvirus-vp3-protein-restricts-the-ifn-%C3%AE-triggered-signaling-pathway-by-inhibiting-stat2-irf9-and-stat2-stat2-complex-formation
#20
Qianqian Peng, Xi Lan, Chen Wang, Yujie Ren, Ningning Yue, Junyong Wang, Bo Zhong, Qiyun Zhu
Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-β-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-β downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9...
April 22, 2017: Virology
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