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https://www.readbyqxmd.com/read/28938623/mifepristone-inhibits-ovarian-cancer-metastasis-by-intervening-in-sdf-1-cxcr4-chemokine-axis
#1
Ning Zheng, Jiahang Chen, Weiqun Liu, Jian Liu, Tao Li, Hongning Chen, Jichuang Wang, Lee Jia
SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations < IC50 inhibited expression of CXCR4 on cell surface of ovarian cancer SKOV-3 and IGROV-1, and reduced expression of the intracellular CXCR4 protein and its related mRNA activated by SDF-1...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938587/transcriptomic-profiles-of-human-foreskin-fibroblast-cells-in-response-to-orf-virus
#2
Daxiang Chen, Mingjian Long, Bin Xiao, Yufeng Xiong, Huiqin Chen, Yu Chen, Zhenzhan Kuang, Ming Li, Yingsong Wu, Daniel L Rock, Daoyuan Gong, Yong Wang, Haijian He, Fang Liu, Shuhong Luo, Wenbo Hao
Orf virus has been utilized as a safe and efficient viral vector against not only diverse infectious diseases, but also against tumors. However, the nature of the genes triggered by the vector in human cells is poorly characterized. Using RNA sequencing technology, we compared specific changes in the transcriptomic profiles in human foreskin fibroblast cells following infection by the orf virus. The results indicated that orf virus upregulates or downregulates expression of a variety of genes, including genes involved in antiviral immune response, apoptosis, cell cycle and a series of signaling pathways, such as the IFN and p53-signaling pathways...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936810/phosphorylated-cxcr4-expression-has-a-positive-prognostic-impact-in-colorectal-cancer
#3
B Weixler, F Renetseder, I Facile, N Tosti, E Cremonesi, A Tampakis, T Delko, S Eppenberger-Castori, A Tzankov, G Iezzi, C Kettelhack, S D Soysal, U von Holzen, G C Spagnoli, L Terracciano, L Tornillo, Raoul A Droeser, S Däster
BACKGROUND: The CXCL12-CXCR4 chemokine axis plays an important role in cell trafficking as well as in tumor progression. In colorectal cancer (CRC), the chemokine receptor CXCR4 has been shown to be an unfavorable prognostic factor in some studies, however, the role of its activated (phosphorylated) form, pCXCR4, has not yet been evaluated. Here, we aimed to investigate the prognostic value of CXCR4 and pCXCR4 in a large cohort of CRC patients. PATIENTS AND METHODS: A tissue microarray (TMA) of 684 patient specimens of primary CRCs was analyzed by immunohistochemistry (IHC) for the expression of CXCR4 and pCXCR4 by tumor cells and tumor-infiltrating immune cells (TICs)...
September 21, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28936426/comparison-of-diabetic-and-non-diabetic-human-leukocytic-responses-to-different-capsule-types-of-klebsiella-pneumoniae-responsible-for-causing-pyogenic-liver-abscess
#4
I Russel Lee, Ethel Sng, Kok-Onn Lee, James S Molton, Monica Chan, Shirin Kalimuddin, Ezlyn Izharuddin, David C Lye, Sophia Archuleta, Yunn-Hwen Gan
The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28936366/constitutive-and-stress-induced-expression-of-ccl5-machinery-in-rodent-retina
#5
D'Anne S Duncan, William M McLaughlin, Noah Vasilakes, Franklin D Echevarria, Cathryn R Formichella, Rebecca M Sappington
Signaling by inflammatory cytokines and chemokines is associated with neurodegeneration in disease and injury. Here we examined expression of the β-chemokine CCL5 and its receptors in the mouse retina and evaluated its relevance in glaucoma, a common optic neuropathy associated with sensitivity to intraocular pressure (IOP). Using quantitative PCR, fluorescent in situ hybridization, immunohistochemistry and quantitative image analysis, we found CCL5 mRNA and protein was constitutively expressed in the inner retina and synaptic layers...
June 2017: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28936214/a-mucosal-and-cutaneous-chemokine-ligand-for-the-lymphocyte-chemoattractant-receptor-gpr15
#6
Borja Ocón, Junliang Pan, Theresa Thu Dinh, Wenjing Chen, Romain Ballet, Michael Bscheider, Aida Habtezion, Hua Tu, Brian A Zabel, Eugene C Butcher
Chemoattractants control lymphocyte recruitment from the blood, contributing to the systemic organization of the immune system. The G protein-linked receptor GPR15 mediates lymphocyte homing to the large intestines and skin. Here we show that the 9 kDa CC-motif containing cationic polypeptide AP57/colon-derived sushi containing domain-2 binding factor (CSBF), encoded by C10orf99 in the human and 2610528A11Rik in the mouse, functions as a chemokine ligand for GPR15 (GPR15L). GPR15L binds GPR15 and attracts GPR15-expressing T cells including lymphocytes in colon-draining lymph nodes and Vγ3(+) thymic precursors of dermal epithelial T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28936211/regulation-of-human-macrophage-m1-m2-polarization-balance-by-hypoxia-and-the-triggering-receptor-expressed-on-myeloid-cells-1
#7
Federica Raggi, Simone Pelassa, Daniele Pierobon, Federica Penco, Marco Gattorno, Francesco Novelli, Alessandra Eva, Luigi Varesio, Mirella Giovarelli, Maria Carla Bosco
Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28936196/anti-inflammatory-targets-for-the-treatment-of-reperfusion-injury-in-stroke
#8
REVIEW
Atsushi Mizuma, Midori A Yenari
While the mainstay of acute stroke treatment includes revascularization via recombinant tissue plasminogen activator or mechanical thrombectomy, only a minority of stroke patients are eligible for treatment, as delayed treatment can lead to worsened outcome. This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I). R/I is occurred when revascularization is delayed after critical brain and vascular injury has occurred, so that when oxygenated blood is restored, ischemic damage is increased, rather than decreased...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28936122/depletion-of-club-cells-attenuates-bleomycin-induced-lung-injury-and-fibrosis-in-mice
#9
Tetsuya Yokoyama, Toyoshi Yanagihara, Kunihiro Suzuki, Naoki Hamada, Kazuya Tsubouchi, Saiko Ogata-Suetsugu, Hironori Mikumo, Chika Ikeda-Harada, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi
BACKGROUND: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been clarified. We previously demonstrated DNA damage in murine bronchioles in the early stages of bleomycin-induced pulmonary fibrosis that subsequently extended to alveolar cells at the advanced stages of the disease. Club cells are progenitor cells for bronchioles and are known to play protective roles against lung inflammation and damage. The aim of the present study was to elucidate the role of club cells in the development of pulmonary fibrosis...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28935977/zebrafish-in-vivo-screening-for-compounds-amplifying-hematopoietic-stem-and-progenitor-cells-preclinical-validation-in-human-cd34-stem-and-progenitor-cells
#10
Guruchandar Arulmozhivarman, Martin Kräter, Manja Wobus, Jens Friedrichs, Elham Pishali Bejestani, Katrin Müller, Katrin Lambert, Dimitra Alexopoulou, Andreas Dahl, Martin Stöter, Marc Bickle, Nona Shayegi, Jochen Hampe, Friedrich Stölzel, Michael Brand, Malte von Bonin, Martin Bornhäuser
The identification of small molecules that either increase the number and/or enhance the activity of human hematopoietic stem and progenitor cells (hHSPCs) during ex vivo expansion remains challenging. We used an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model and identified histone deacetylase inhibitors (HDACIs), particularly valproic acid (VPA), as significant enhancers of the number of phenotypic HSPCs, both in vivo and during ex vivo expansion. The long-term functionality of these expanded hHSPCs was verified in a xenotransplantation model with NSG mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935759/lymphangiogenesis-facilitates-initial-lymph-formation-and-enhances-the-dendritic-cell-mobilizing-chemokine-ccl21-without-affecting-migration
#11
Tine V Karlsen, Tore Reikvam, Anne Tofteberg, Elham Nikpey, Trude Skogstrand, Marek Wagner, Olav Tenstad, Helge Wiig
OBJECTIVE: Lymphatic vessels play an important role in body fluid, as well as immune system homeostasis. Although the role of malfunctioning or missing lymphatics has been studied extensively, less is known on the functional consequences of a chronically expanded lymphatic network or lymphangiogenesis. APPROACH AND RESULTS: To this end, we used K14-VEGF-C (keratin-14 vascular endothelial growth factor-C) transgenic mice overexpressing the vascular endothelial growth factor C in skin and investigated the responses to inflammatory and fluid volume challenges...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935682/role-of-eosinophils-in-the-initiation-and-progression-of-pancreatitis-pathogenesis
#12
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Anil Mishra
Eosinophilic pancreatitis (EP) is reported in human; however, the etiology and the role of eosinophils in EP pathogenesis is a poorly understood and not excusably explored. Therefore, it is interesting to examine the role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Therefore, we performed real time PCR, ELISA, western blot, anti-MBP immunostaining, Chloroesterase and Massons' trichrome analysis were performed to examine transcript and protein levels of eosinophil active cytokines, chemokines, eosinophils, mast cells and collagen tissue accumulation...
September 21, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28935640/attenuation-of-pulmonary-ace2-activity-impairs-inactivation-of-des-arg9-bradykinin-bkb1r-axis-and-facilitates-lps-induced-neutrophil-infiltration
#13
Chhinder P Sodhi, Christine Wohlford-Lenane, Yukihiro Yamaguchi, Thomas Prindle, William B Fulton, Sanxia Wang, Paul B McCray, Mark C Chappell, David J Hackam, Hongpeng Jia
Angiotensin converting enzyme 2 (ACE2) is a terminal carboxypeptidase with important functions in the renin angiotensin system and plays a critical role in inflammatory lung diseases. ACE2 cleaves single terminal residues from several bioactive peptides such as angiotensin II. However, few of its substrates in the respiratory tract have been identified and the mechanism underlying the role of ACE2 in inflammatory lung disease has not been fully characterized. In an effort to identify biological targets of ACE2 in the lung, we tested its effects on des-arg9 bradykinin (DABK) in airway epithelial cells based upon a hypothesis that DABK is a biological substrate of ACE2 in the lung and ACE2 plays an important role in the pathogenesis of acute lung inflammation partly through modulating DABK/BKB1R axis signaling...
September 21, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28935577/human-pancreatic-acinar-cells-proteomic-characterization-physiologic-responses-and-organellar-disorders-in-ex-vivo-pancreatitis
#14
Aurelia Lugea, Richard T Waldron, Olga A Mareninova, Natalia Shalbueva, Nan Deng, Hsin-Yuan Su, Diane D Thomas, Elaina K Jones, Scott W Messenger, Jiayue Yang, Cheng Hu, Ilya Gukovsky, Zhenqiu Liu, Guy E Groblewski, Anna S Gukovskaya, Fred S Gorelick, Stephen J Pandol
Knowledge of the molecular mechanisms of acute pancreatitis is largely based on studies using rodents. To assess similar mechanisms in humans, we performed ex vivo pancreatitis studies in human acini isolated from cadaveric pancreata from organ donors. Since data on these human acinar preparations are sparse, we assessed their functional integrity, and cellular and organellar morphology using light, fluorescence and electron microscopy; and their proteome by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28935574/taurocholate-induces-biliary-differentiation-of-liver-progenitor-cells-causing-hepatic-stellate-cell-chemotaxis-in-the-ductular-reaction-role-in-pediatric-cystic-fibrosis-liver-disease
#15
Katarzyna N Pozniak, Michael A Pearen, Tamara N Pereira, Cynthia Sm Kramer, Priyakshi Kalita-De Croft, Sujeevi K Nawaratna, Manuel A Fernandez-Rojo, Geoffrey N Gobert, Janina Ee Tirnitz-Parker, John K Olynyk, Ross W Shepherd, Peter J Lewindon, Grant A Ramm
Cystic fibrosis liver disease (CFLD) in children causes progressive fibrosis leading to biliary cirrhosis, however its cause(s) and early pathogenesis are unclear. We hypothesised that a bile acid-induced Ductular Reaction (DR) drives fibrogenesis. We evaluated the DR by cytokeratin-7 immunohistochemistry in liver biopsies, staged for fibrosis, from 60 children with CFLD and demonstrated that the DR was significantly correlated with hepatic fibrosis stage and biliary taurocholate levels. To examine the mechanisms involved in DR induction liver progenitor cells (LPCs) were treated with taurocholate and key events in DR evolution were assessed: LPC proliferation, LPC biliary differentiation and hepatic stellate cell (HSC) chemotaxis...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28935522/beyond-chemoattraction-multifunctionality-of-chemokine-receptors-in-leukocytes
#16
REVIEW
Pilar López-Cotarelo, Carolina Gómez-Moreira, Olga Criado-García, Lucas Sánchez, José Luis Rodríguez-Fernández
The word chemokine is a combination of the words chemotactic and cytokine, in other words cytokines that promote chemotaxis. Hence, the term chemokine receptor refers largely to the ability to regulate chemoattraction. However, these receptors can modulate additional leukocyte functions, as exemplified by the case of CCR7 which, apart from chemotaxis, regulates survival, migratory speed, endocytosis, differentiation and cytoarchitecture. We present evidence highlighting that multifunctionality is a common feature of chemokine receptors...
September 18, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28934917/sparse-supervised-classification-methods-predict-and-characterize-nanomaterial-exposures-independent-markers-of-mwcnt-exposures
#17
Naveena Yanamala, Marlene S Orandle, Vamsi K Kodali, Lindsey Bishop, Patti C Zeidler-Erdely, Jenny R Roberts, Vincent Castranova, Aaron Erdely
Recent experimental evidence indicates significant pulmonary toxicity of multiwalled carbon nanotubes (MWCNTs), such as inflammation, interstitial fibrosis, granuloma formation, and carcinogenicity. Although numerous studies explored the adverse potential of various CNTs, their comparability is often limited. This is due to differences in administered dose, physicochemical characteristics, exposure methods, and end points monitored. Here, we addressed the problem through sparse classification method, a supervised machine learning approach that can reduce the noise contained in redundant variables for discriminating among MWCNT-exposed and MWCNT-unexposed groups...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28934227/hemorrhage-enhances-cytokine-complement-component-3-and-caspase-3-and-regulates-micrornas-associated-with-intestinal-damage-after-whole-body-gamma-irradiation-in-combined-injury
#18
Juliann G Kiang, Joan T Smith, Marsha N Anderson, Thomas B Elliott, Paridhi Gupta, Nagaraja S Balakathiresan, Radha K Maheshwari, Barbara Knollmann-Ritschel
Hemorrhage following whole-body γ-irradiation in a combined injury (CI) model increases mortality compared to whole-body γ-irradiation alone (RI). The decreased survival in CI is accompanied by increased bone marrow injury, decreased hematocrit, and alterations of miRNA in the kidney. In this study, our aim was to examine cytokine homeostasis, susceptibility to systemic bacterial infection, and intestinal injury. More specifically, we evaluated the interleukin-6 (IL-6)-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), Flt-3 ligand, and corticosterone...
2017: PloS One
https://www.readbyqxmd.com/read/28933920/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#19
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy Sc Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma, and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (mild, moderate and severe asthma; N=46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips and results were validated by real-time quantitative PCR...
September 21, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28933704/the-association-between-serum-cytokine-and-chemokine-levels-and-antiviral-response-by-entecavir-treatment-in-chronic-hepatitis-b-patients
#20
Mio Kurihara, Masataka Tsuge, Eisuke Murakami, Nami Mori, Waka Ohishi, Takuro Uchida, Hatsue Fujino, Takashi Nakahara, Hiromi Abe-Chayama, Tomokazu Kawaoka, Daiki Miki, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Hiroshi Aikata, Hidenori Ochi, Yizhou Zhang, Grace Naswa Makokha, C Nelson Hayes, Kazuaki Chayama
BACKGROUND: Although Nucleos(t)ide analogue therapy is thought to suppress chronic hepatitis B(CHB) via regulation of inflammatory cytokines/chemokines, the mechanism is still unclear. In this study, serum cytokine/chemokine levels were measured in CHB patients treated with entecavir, and the association with antiviral response was analyzed. METHODS: Seventy-eight Japanese patients with CHB were enrolled, and serum cytokine/chemokine levels were measured at baseline and at 12, 24, and 48 weeks of entecavir treatment using the MULTIPLEX kit...
September 21, 2017: Antiviral Therapy
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