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https://www.readbyqxmd.com/read/29790398/acute-inflammatory-biomarker-responses-to-diffuse-traumatic-brain-injury-in-the-rat-monitored-by-a-novel-microdialysis-technique
#1
Fredrik Clausen, Niklas Marklund, Lars Hillered
Neuroinflammation is a major contributor to the progressive brain injury process induced by traumatic brain injury (TBI), and may play an important role in the pathophysiology of axonal injury. The immediate neuroinflammatory cascade cannot be characterized in the human setting. Therefore, we used the midline fluid percussion injury model of diffuse TBI in rats and a novel microdialysis (MD) method providing stable diffusion-driven biomarker sampling. Immediately post-injury, bilateral amphiphilic tri-block polymer coated MD probes (100 kDa cut off membrane) were inserted and perfused with Dextran 500 kDa-supplemented artificial CSF to optimize protein capture...
May 23, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29787561/interplay-of-strain-and-race-ethnicity-in-the-innate-immune-response-to-m-tuberculosis
#2
P Nahid, L G Jarlsberg, M Kato-Maeda, M R Segal, D H Osmond, S Gagneux, K Dobos, M Gold, P C Hopewell, D M Lewinsohn
BACKGROUND: The roles of host and pathogen factors in determining innate immune responses to M. tuberculosis are not fully understood. In this study, we examined host macrophage immune responses of 3 race/ethnic groups to 3 genetically and geographically diverse M. tuberculosis lineages. METHODS: Monocyte-derived macrophages from healthy Filipinos, Chinese and non-Hispanic White study participants (approximately 45 individuals/group) were challenged with M. tuberculosis whole cell lysates of clinical strains Beijing HN878 (lineage 2), Manila T31 (lineage 1), CDC1551 (lineage 4), the reference strain H37Rv (lineage 4), as well as with Toll-like receptor 2 agonist lipoteichoic acid (TLR2/LTA) and TLR4 agonist lipopolysaccharide (TLR4/LPS)...
2018: PloS One
https://www.readbyqxmd.com/read/29783988/tolerogenic-bone-marrow-derived-dendritic-cells-induce-neuroprotective-regulatory-t-cells-in-a-model-of-parkinson-s-disease
#3
Charles R Schutt, Howard E Gendelman, R Lee Mosley
BACKGROUND: Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Recently, we demonstrated in an early phase 1 clinical trial that GM-CSF also improves motor skills in PD patients. However, the mechanisms of Treg induction and its effects on neuroprotective responses remain unknown...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29783918/rituximab-mediated-late-onset-neutropenia-in-systemic-lupus-erythematosus-distinct-roles-of-baff-and-april
#4
I Parodis, F Söder, F Faustini, Z Kasza, I Samuelsson, A Zickert, E Svenungsson, R F van Vollenhoven, V Malmström, F Wermeling, I Gunnarsson
Objective Rituximab-mediated late-onset neutropenia (LON) has been described in various diseases. We investigated its occurrence, consequences and contributing factors in patients with systemic lupus erythematosus (SLE). Methods Rituximab-treated patients from the Karolinska University Hospital ( n = 107) were surveyed. LON was defined as an absolute neutrophil count <1500 cells/μl, occurring four weeks to two years following rituximab treatment, or later during sustained B-cell depletion. Serum levels of B-cell-related cytokines and growth factors of the myeloid lineage were determined using enzyme-linked immunosorbent assay...
January 1, 2018: Lupus
https://www.readbyqxmd.com/read/29782314/a-retrospective-belgian-multi-center-mri-biomarker-study-in-alzheimer-s-disease-remember
#5
Ellis Niemantsverdriet, Annemie Ribbens, Christine Bastin, Florence Benoit, Bruno Bergmans, Jean-Christophe Bier, Roxanne Bladt, Lene Claes, Peter Paul De Deyn, Olivier Deryck, Bernard Hanseeuw, Adrian Ivanoiu, Jean-Claude Lemper, Eric Mormont, Gaëtane Picard, Eric Salmon, Kurt Segers, Anne Sieben, Dirk Smeets, Hanne Struyfs, Evert Thiery, Jos Tournoy, Eric Triau, Anne-Marie Vanbinst, Jan Versijpt, Maria Bjerke, Sebastiaan Engelborghs
BACKGROUND: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. METHODS: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29780382/extracellular-purine-metabolism-is-the-switchboard-of-immunosuppressive-macrophages-and-a-novel-target-to-treat-diseases-with-macrophage-imbalances
#6
Anna Ohradanova-Repic, Christian Machacek, Celine Charvet, Franck Lager, Delphine Le Roux, René Platzer, Vladimir Leksa, Goran Mitulovic, Thomas R Burkard, Gerhard J Zlabinger, Michael B Fischer, Vincent Feuillet, Gilles Renault, Stephan Blüml, Miroslav Benko, Miloslav Suchanek, Johannes B Huppa, Takami Matsuyama, Artur Cavaco-Paulo, Georges Bismuth, Hannes Stockinger
If misregulated, macrophage (Mϕ)-T cell interactions can drive chronic inflammation thereby causing diseases, such as rheumatoid arthritis (RA). We report that in a proinflammatory environment, granulocyte-Mϕ (GM-CSF)- and Mϕ colony-stimulating factor (M-CSF)-dependent Mϕs have dichotomous effects on T cell activity. While GM-CSF-dependent Mϕs show a highly stimulatory activity typical for M1 Mϕs, M-CSF-dependent Mϕs, marked by folate receptor β (FRβ), adopt an immunosuppressive M2 phenotype. We find the latter to be caused by the purinergic pathway that directs release of extracellular ATP and its conversion to immunosuppressive adenosine by co-expressed CD39 and CD73...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779831/interleukin-6-significantly-improves-predictive-value-of-systemic-inflammatory-response-syndrome-for-predicting-severe-acute-pancreatitis
#7
Saransh Jain, Shallu Midha, Soumya Jagannath Mahapatra, Swatantra Gupta, Manish Kumar Sharma, Baibaswata Nayak, Tony George Jacob, Shalimar, Pramod Kumar Garg
BACKGROUND: Predicting severe acute pancreatitis (AP) is important for triage, prognosis, and designing therapeutic trials. Persistent systemic inflammatory response syndrome (SIRS) predicts severe AP but its diagnostic accuracy is suboptimal. Our objective was to study if cytokine levels could improve the predictive value of clinical variables for the development of severe AP. METHODS: Consecutive patients with AP were included in a prospective cohort study at a tertiary care center...
May 14, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29778648/impact-of-insulin-on-the-intestinal-microcirculation-in-a-model-of-sepsis-related-hyperglycemia
#8
Alexa Caldwell, Jan Niklas Morick, Anne-Marie Jentsch, Annette Wegener, Dragan Pavlovic, Nadia Al-Banna, Christian Lehmann
BACKGROUND: Sepsis involves dysfunctional glucose metabolism. Among patients with sepsis, hyperglycemia is frequent and insulin administration has been evaluated for glycemic control to improve patient outcomes. Only few studies have examined the hyperglycemic microcirculation and the impact of insulin on the microvasculature in sepsis. OBJECTIVE: To study the functional capillary density (FCD) and leukocyte activation within the intestinal microcirculation in endotoxin-induced experimental sepsis...
May 17, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29777594/il-3-producing-basophils-are-required-to-exacerbate-airway-hyper-responsiveness-in-a-murine-inflammatory-model
#9
Rachel Rignault-Bricard, François Machavoine, Salah Mecheri, Olivier Hermine, Elke Schneider, Michel Dy, Maria Leite-de-Moraes
BACKGROUND: Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro-Th2 cytokines and histamine. However, the mechanisms through which bone marrow-resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL-3 in promoting pro-Th2 basophils. METHODS: BMRB and basophils exposed to IL-3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels...
May 19, 2018: Allergy
https://www.readbyqxmd.com/read/29776615/a-new-and-efficient-culture-method-for-porcine-bone-marrow-derived-m1-and-m2-polarized-macrophages
#10
Jiye Gao, Maaike R Scheenstra, Albert van Dijk, Edwin J A Veldhuizen, Henk P Haagsman
BACKGROUND: Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. METHODS: Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively...
June 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29774106/hematopoietic-restricted-ptpn11e76k-reveals-indolent-mpn-progression-in-mice
#11
Stefan P Tarnawsky, Wen-Mei Yu, Cheng-Kui Qu, Rebecca J Chan, Mervin C Yoder
Juvenile Myelomonocytic Leukemia (JMML) is a pediatric myeloproliferative neoplasm (MPN) that has a poor prognosis. Somatic mutations in Ptpn11 are the most frequent cause of JMML and they commonly occur in utero . Animal models of mutant Ptpn11 have probed the signaling pathways that contribute to JMML. However, existing models may inappropriately exacerbate MPN features by relying on non-hematopoietic-restricted Cre-loxP strains or transplantations into irradiated recipients. In this study we generate hematopoietic-restricted models of Ptpn11E76K-mediated disease using Csf1r-MCM and Flt3Cre...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#12
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772098/insights-in-particulate-matter-induced-allergic-airway-inflammation-focus-on-the-epithelium
#13
Katrien C De Grove, Sharen Provoost, Guy G Brusselle, Guy F Joos, Tania Maes
Outdoor air pollution is a major environmental health problem throughout the world. In particular, exposure to particulate matter (PM) has been associated with the development and exacerbation of several respiratory diseases, including asthma. Although the adverse health effects of PM have been demonstrated for many years, the underlying mechanisms have not been fully identified. In this review, we focus on the role of the lung epithelium and specifically highlight multiple cytokines in PM-induced respiratory responses...
May 17, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#14
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771377/alternative-splicing-analysis-in-human-monocytes-and-macrophages-reveals-mbnl1-as-major-regulator
#15
Hongfei Liu, Paolo A Lorenzini, Fan Zhang, Shaohai Xu, Mei Su M Wong, Jie Zheng, Xavier Roca
We report the detailed transcriptomic profiles of human innate myeloid cells using RNA sequencing. Monocytes migrate from blood into infected or wounded tissue to differentiate into macrophages, and control inflammation via phagocytosis or cytokine secretion. We differentiated culture primary monocytes with either GM- or M-CSF to obtain pro- or anti-inflammatory macrophages, and respectively activated them with either LPS/IFNγ or anti-inflammatory cytokines. We also treated the THP-1 monocytic cell line with PMA and similar cytokines to mimic differentiation and activation...
May 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29770894/efficacy-of-punarnavine-in-restraining-organ-specific-tumour-progression-in-4t1-induced-murine-breast-tumour-model
#16
Gilcy George Kallivalappil, Girija Kuttan
Most of the breast cancer deaths occur when cancer cells depart from their tumour of origin and spread systemically and colonise distant organs. The present study was to find out whether punarnavine, the quinolizidine alkaloid, with already proven antimetastatic effect on spontaneous B16F10 pulmonary metastasis has got any effect on a drastic organ-specific breast cancer spread. For the study, we selected a syngenic mouse 4T1 breast tumour model that mimics stage four of human breast cancer. The metastatic progression of 4T1 to lymph nodes, lungs, and liver was reduced by punarnavine (40 mg/kg body weight) administration in BALB/c mice...
May 17, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29770533/nctd-enhances-antitumor-immunity-of-gm-csf-prostate-cancer-cells-vaccine-by-inducing-apoptosis-of-regulatory-t-cells
#17
Lijun Mo, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
Norcantharidin (NCTD) is a promising antitumor drug with low toxicity. It was reported to be able to regulate immunity, but the mechanism is not yet clear. Here we explored whether NCTD could enhance the antitumor immunity induced by prostate cancer cells vaccine. The results in vitro study showed that NCTD induced apoptosis and inhibited proliferation of Tregs. Mechanistic research showed that NCTD inhibited Akt activation and activated FOXO1 transcription, resulting in pro-apoptotic effect. The results in vivo study showed that more tumor-infiltrating Tregs existed within peripheral blood and tumor tissue after treating with the vaccine...
May 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29770434/tumor-yap1-and-pten-expression-correlates-with-tumor-associated-myeloid-suppressor-cell-expansion-and-reduced-survival-in-colorectal-cancer
#18
Rong Yang, Ting-Ting Cai, Xiao-Jun Wu, Yi-Na Liu, Jia He, Xiao-Shi Zhang, Gang Ma, Jiang Li
The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33+ MDSC number and YAP1 and PTEN levels in CRC patients (P < 0.05). Moreover, the CD33+ MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0.05). Notably, CD33+ MDSCs were an independent survival predictor for CRC patients through a Cox model analysis. In vitro data determined that the expression levels of YAP1 and PTEN in CRC-derived cell lines were associated with CRC-derived MDSC induction, and the blockade of YAP1 and PTEN decreased CRC-derived MDSC induction...
May 16, 2018: Immunology
https://www.readbyqxmd.com/read/29769377/-ex-vivo-cytokine-release-determined-by-a-multiplex-cytokine-assay-in-response-to-coccidioidal-antigen-stimulation-of-whole-blood-among-subjects-with-recently-diagnosed-primary-pulmonary-coccidioidomycosis
#19
Neil M Ampel, Ian Robey, Chinh T Nguyen, Brentin Roller, Jessica August, Kenneth S Knox, Demosthenes Pappagianis
The elements of the cellular immune response in human coccidioidomycosis remain undefined. We examined the ex vivo release of an array of inflammatory proteins in response to incubation with a coccidioidal antigen preparation to ascertain which of these might be associated with diagnosis and outcome. Patients with a recent diagnosis of primary pulmonary coccidioidomycosis and a control group of healthy subjects were studied. Blood samples were incubated for 18 h with T27K, a soluble coccidioidal preparation containing multiple glycosylated antigens, and the supernatant was assayed for inflammatory proteins using the multiplex Luminex system...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29765986/advanced-glycation-end-products-enhance-murine-monocyte-proliferation-in-bone-marrow-and-prime-them-into-an-inflammatory-phenotype-through-mapk-signaling
#20
Xian Jin, Liang Liu, Yaping Zhang, Yin Xiang, Guizhi Yin, Yi Lu, Ludong Shi, Jian Dong, Chengxing Shen
Objective: Increased monocytes, particularly the inflammatory subset, are associated with accelerated atherosclerosis in diabetes through thus far incompletely defined mechanisms. The present study tested the hypothesis that advanced glycation end products (AGEs) promote bone marrow monocytes to proliferate and drive them into an inflammatory phenotype. Methods and Results: In vivo, AGEs (25 mg/kg i.p. for 7 days) increased proportions of CD115+ monocytes and the inflammatory subset, the CD115+ Ly6Chigh cells, in murine bone marrow (flow cytometry analysis (FCM)), and enhanced gene expression of proinflammatory cytokines (IL-1 β and TNF- α ) but only slightly upregulated mRNA expression of anti-inflammatory cytokine (IL-10) (real-time PCR) in monocytes...
2018: Journal of Diabetes Research
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