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https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#1
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28600970/thp-1-and-human-peripheral-blood-mononuclear-cell-derived-macrophages-differ-in-their-capacity-to-polarize-in-vitro
#2
Hiromi Shiratori, Carmen Feinweber, Sonja Luckhardt, Bona Linke, Eduard Resch, Gerd Geisslinger, Andreas Weigert, Michael J Parnham
Macrophages (Mφ) undergo activation to pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to pathophysiologic stimuli and dysregulation of the M1-M2 balance is often associated with diseases. Therefore, studying mechanisms of macrophage polarization may reveal new drug targets. Human Mφ polarization is generally studied in primary monocyte-derived Mφ (PBMC Mφ) and THP-1-derived Mφ (THP-1 Mφ). We compared the polarization profile of THP-1 Mφ with that of PBMC Mφ to assess the alternative use of THP-1 for polarization studies...
June 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28594935/a-nested-case-control-study-of-277-prediagnostic-serum-cytokines-and-glioma
#3
Judith Schwartzbaum, Min Wang, Elisabeth Root, Maciej Pietrzak, Grzegorz A Rempala, Ruo-Pan Huang, Tom Borge Johannesen, Tom K Grimsrud
Recent research shows bidirectional communication between the normal brain and the peripheral immune system. Glioma is a primary brain tumor characterized by systemic immunosuppression. To better understand gliomagenesis, we evaluated associations between 277 prediagnostic serum cytokines and glioma. We used glioma (n = 487) and matched control (n = 487) specimens from the Janus Serum Bank Cohort in Oslo, Norway. Conditional logistic regression allowed us to identify those cytokines that were individually associated with glioma...
2017: PloS One
https://www.readbyqxmd.com/read/28526296/mesenchymal-stem-cells-mscs-attenuate-cutaneous-sclerodermatous-graft-versus-host-disease-scl-gvhd-through-inhibition-of-immune-cell-infiltration-in-a-mouse-model
#4
Ji-Young Lim, Da-Bin Ryu, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. The clinical and pathological severity of cutaneous Scl-GVHD was significantly attenuated in MSC-treated recipients relative to Scl-GVHD controls. After MSC treatment, skin collagen production was significantly reduced with consistent downregulation of TGF-β expression...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28501670/treg-recruiting-microspheres-prevent-inflammation-in-a-murine-model-of-dry-eye-disease
#5
Michelle L Ratay, Andrew J Glowacki, Stephen C Balmert, Abhinav P Acharya, Julia Polat, Lawrence P Andrews, Morgan V Fedorchak, Joel S Schuman, Dario A A Vignali, Steven R Little
Dry eye disease (DED) is a common ocular disorder affecting millions of individuals worldwide. The pathology of DED involves the infiltration of CD4(+) lymphocytes, leading to tear film instability and destructive inflammation. In the healthy steady state, a population of immunosuppressive T-cells called regulatory T-cells (Treg) regulates proliferation of immune cells that would otherwise lead to a disruption of immunological homeostasis. For this reason, it has been suggested that Tregs could restore the immunological imbalance in DED...
May 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28501127/c-c-motif-chemokine-22-ligand-ccl22-concentrations-in-sera-of-gastric-cancer-patients-are-related-to-peritoneal-metastasis-and-predict-recurrence-within-one-year-after-radical-gastrectomy
#6
Yuzhe Wei, Tie Wang, Hongjiang Song, Lining Tian, Gongwei Lyu, Lei Zhao, Yingwei Xue
BACKGROUND: Gastric cancer is a common cancer with a poor prognosis. Chemokines play important roles in the tumor microenvironments to support tumor growth and metastasis. The effects of C-C motif chemokine ligand 22 (CCL22) in gastric cancer remain unclear. MATERIALS AND METHODS: Between January 1, 2014 and April 31, 2014, a total of 298 gastric cancer patients were recruited to this study. Circulating concentrations of CCL22 were measured in gastric cancer patients before surgery, at discharged and during follow-up visits...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28493293/responsiveness-to-oral-prednisolone-in-severe-asthma-is-related-to-the-degree-of-eosinophilic-airway-inflammation
#7
Ana R Sousa, Richard P Marshall, Linda C Warnock, Sarah Bolton, Annette Hastie, Fiona Symon, Beverley Hargadon, Hilary Marshall, Matthew Richardson, Christopher E Brightling, Pranab Haldar, Roberta Milone, Peter Chalk, Rick Williamson, Reynold Panettieri, Richard Knowles, Eugene R Bleecker, Andrew J Wardlaw
BACKGROUND: Patients with severe asthma appear relatively corticosteroid resistant. Corticosteroid responsiveness is closely related to the degree of eosinophilic airway inflammation. The extent to which eosinophilic airway inflammation in severe asthma responds to treatment with systemic corticosteroids is not clear. OBJECTIVE: To relate the physiological and inflammatory response to systemic corticosteroids in asthma to disease severity and the baseline extent of eosinophilic inflammation...
May 10, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28487256/lipopolysaccharide-lps-induced-pulmonary-neutrophil-recruitment-and-platelet-activation-is-mediated-via-the-p2y1-and-p2y14-receptors-in-mice
#8
R T Amison, S Arnold, B G O'Shaughnessy, S J Cleary, J Ofoedu, M Idzko, C P Page, S C Pitchford
Platelet activation occurs during host defence and in various inflammatory disorders. In animal models of infection and inflammation, experimental depletion of platelets leads to significantly reduced leukocyte recruitment and impaired clearance of pathogens from the lung. It is now appreciated that purinergic receptor activation is required for leukocyte activation, motility and adhesion, and platelet interactions with leukocytes can be modulated by purinergic stimulation of platelets. Here, we have investigated the role of platelet P2Y1, P2Y12, P2Y14, and P2X1 receptors on leukocyte recruitment and chemotaxis...
May 6, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28487109/ccr4-mediated-chemotaxis-of-regulatory-t-cells-suppress-the-activation-of-t-cells-and-nk-cells-via-tgf-%C3%AE-pathway-in-human-non-small-cell-lung-cancer
#9
Wei Liu, Xinyi Wei, Lin Li, Xiaobin Wu, Junli Yan, Hui Yang, Fangzhou Song
C-C chemokine receptor type 4 has been reported to correlate with lung cancer. However, the role of CCR4 in human non-small cell lung cancer patients is not well defined. Here, we demonstrated that increased expression of CCR4 was associated with clinical stage and CCR4 was an independent risk factor for overall survival in NSCLC patients. Moreover, tumor-infiltrating Treg cells were higher expression than matched adjacent tissues in CCR4+ NSCLC. Higher expression of chemokine CCL17 and CCL22 could recruit Treg cells to tumor sites in NSCLC...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28481241/biomarker-and-histopathology-evaluation-of-patients-with-recurrent-glioblastoma-treated-with-galunisertib-lomustine-or-the-combination-of-galunisertib-and-lomustine
#10
David Capper, Andreas von Deimling, Alba A Brandes, Antoine F Carpentier, Santosh Kesari, Juan M Sepulveda-Sanchez, Helen R Wheeler, Olivier Chinot, Lawrence Cher, Joachim P Steinbach, Pol Specenier, Jordi Rodon, Ann Cleverly, Claire Smith, Ivelina Gueorguieva, Colin Miles, Susan C Guba, Durisala Desaiah, Shawn T Estrem, Michael M Lahn, Wolfgang Wick
Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations...
May 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28466432/macrophage-subset-expressing-cd169-in-peritoneal-cavity-regulated-mucosal-inflammation-together-with-lower-levels-of-ccl22
#11
Dan Wang, Qiuting Li, Yang Yang, Shengyu Hao, Xiaolei Han, Jia Song, Yue Yin, Xiangzhi Li, Masato Tanaka, Chun-Hong Qiu
Crohn's disease (CD) and ulcerative colitis (UC) are the most widely known types of inflammatory bowel diseases (IBD) and have been paid more attention due to their increasing incidence and a substantial increase in the risk of colorectal cancer (CRC). However, the phenotype and, more importantly, the function in the regulation of mucosal inflammation by different macrophages are poorly understood, even though macrophages constitute a major subset of intestinal myeloid cells. The results firstly showed that the subset of peritoneal CD11b(+)CD169(+) macrophages increased and CCL22 expression level decreased significantly during the DSS-induced colitis...
May 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28445949/lmp1-slamf1high-cells-are-associated-with-drug-resistance-in-epstein-barr-virus-positive-farage-cells
#12
Heejei Yoon, Young Hyeh Ko
How Epstein-Barr virus (EBV) affects the clinical outcome of EBV-positive diffuse large B-cell lymphoma (DLBCL) remains largely unknown. The viral oncogene LMP1 is at the crux of tumorigenesis and cell survival. Therefore, we examined the association between LMP1high cells drug resistance. We first assessed SLAMF1 as a surrogate marker for LMP1high cells. LMP1 and its target gene CCL22 were highly expressed in SLAMF1high Farage cells. These cells survived longer following treatment with a combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440453/scrg1-suppresses-lps-induced-ccl22-production-through-erk1-2-activation-in-mouse-macrophage-raw264-7-cells
#13
Manabu Inoue, Junko Yamada, Emiko Aomatsu-Kikuchi, Kazuro Satoh, Hisatomo Kondo, Akira Ishisaki, Naoyuki Chosa
Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self‑renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity of SCRG1 in macrophages. The mouse macrophage‑like cell line Raw264.7 expressed BST1/β1 or BST1/β2 integrin as possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell proliferation, migration, or adhesion in these macrophages...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28438174/exercise-attenuates-neurological-deficits-by-stimulating-a-critical-hsp70-nf-%C3%AE%C2%BAb-il-6-synapsin-i-axis-in-traumatic-brain-injury-rats
#14
Chung-Ching Chio, Hung-Jung Lin, Yu-Feng Tian, Yu-Chieh Chen, Mao-Tsun Lin, Cheng-Hsien Lin, Ching-Ping Chang, Chien-Chin Hsu
BACKGROUND: Despite previous evidence for a potent inflammatory response after a traumatic brain injury (TBI), it is unknown whether exercise preconditioning (EP) improves outcomes after a TBI by modulating inflammatory responses. METHODS: We performed quantitative real-time PCR (qPCR) to quantify the genes encoding 84 cytokines and chemokines in the peripheral blood and used ELISA to determine both the cerebral and blood levels of interleukin-6 (IL-6). We also performed the chromatin immunoprecipitation (ChIP) assay to evaluate the extent of nuclear factor kappa-B (NF-κB) binding to the DNA elements in the IL-6 promoter regions...
April 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28415693/ccr4-is-a-determinant-of-melanoma-brain-metastasis
#15
Anat Klein, Orit Sagi-Assif, Tsipi Meshel, Alona Telerman, Sivan Izraely, Shlomit Ben-Menachem, Jagadeesh Bayry, Diego M Marzese, Shuichi Ohe, Dave S B Hoon, Neta Erez, Isaac P Witz
We previously identified the chemokine receptor CCR4 as part of the molecular signature of melanoma brain metastasis. The aim of this study was to determine the functional significance of CCR4 in melanoma brain metastasis. We show that CCR4 is more highly expressed by brain metastasizing melanoma cells than by local cutaneous cells from the same melanoma. Moreover, we found that the expression of CCR4 is significantly higher in paired clinical specimens of melanoma metastases than in samples of primary tumors from the same patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408751/mmp9-integrates-multiple-immunoregulatory-pathways-that-discriminate-high-suppressive-activity-of-human-mesenchymal-stem-cells
#16
Carolina Lavini-Ramos, Hernandez Moura Silva, Alessandra Soares-Schanoski, Sandra Maria Monteiro, Ludmila Rodrigues Pinto Ferreira, Ana Paula Pacanaro, Samirah Gomes, Janaína Batista, Kellen Faé, Jorge Kalil, Verônica Coelho
The mechanisms underlying mesenchymal stem cells' (MSC) suppressive potency are largely unknown. We here show that highly suppressive human adipose tissue-derived MSC (AdMSC) display and induce a differential immunologic profile, upon ongoing AdMSC suppressive activity, promoting: (i) early correlated inhibition of IFN-γ and TNF-α production, along IL-10 increase, (ii) CD73(+)Foxp3(+)Treg subset expansion, and (iii) specific correlations between gene expression increases, such as: MMP9 correlated with CCL22, TNF, FASL, RUNX3, and SEMAD4 in AdMSC and, in T cells, MMP9 upregulation correlated with CCR4, IL4 and TBX21, among others, whereas MMP2 correlated with BCL2 and LRRC31...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28399391/cd163-positive-macrophages-within-the-tumor-stroma-are-associated-with-lymphangiogenesis-and-lymph-node-metastasis-in-oral-squamous-cell-carcinoma
#17
Yuko Yamagata, Hirofumi Tomioka, Kei Sakamoto, Kiyoshi Sato, Hiroyuki Harada, Tohru Ikeda, Kou Kayamori
PURPOSE: Increasing evidence shows that tumor stromal components, particularly tumor-associated macrophages (TAMs), play an important role in the tumor progression of various solid malignant tumor types. However, their roles in oral squamous cell carcinoma (OSCC) have not been fully elucidated. MATERIALS AND METHODS: Seventy human tongue OSCC samples were analyzed in the present study. Immunohistochemistry was used to investigate the correlations between the densities of CD68-, CD163-, and CD204-positive TAMs and clinicopathologic parameters...
March 18, 2017: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28387445/stimulation-of-oral-fibroblast-chemokine-receptors-identifies-ccr3-and-ccr4-as-potential-wound-healing-targets
#18
Jeroen K Buskermolen, Sanne Roffel, Susan Gibbs
The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts...
April 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28383711/synergistic-effect-of-regulatory-t-cells-and-proinflammatory-cytokines-in-angiogenesis-in-the-endometriotic-milieu
#19
Xiao-Qiu Wang, Wen-Jie Zhou, Xue-Zhen Luo, Yu Tao, Da-Jin Li
STUDY QUESTION: Do regulatory T cells (Tregs) contribute to angiogenesis in endometriosis? SUMMARY ANSWER: High levels of CCL17 and CCL22 cause the recruitment of Tregs, upregulate the immunosuppression of Tregs and, in turn, may promote angiogenesis in endometrial cells in synergy with proinflammatory cytokines. WHAT IS ALREADY KNOWN: The peritoneal fluid of patients with endometriosis has a higher percentage of Tregs than that of normal individuals; however, the regulatory role of Tregs in the disease remains unclear...
June 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28374494/immunogenetic-profiling-of-23-snps-of-cytokine-and-chemokine-receptor-genes-through-a-minisequencing-technique-design-development-and-validation
#20
J M Valverde-Villegas, R M de Medeiros, S E M Almeida, J A B Chies
The minisequencing technique offers accuracy and robustness to genotyping of polymorphic DNA variants, being an excellent option for the identification and analyses of prognostic/susceptibility markers in human diseases. Two multiplex minisequencing assays were designed and standardized to screen 23 candidate SNPs in cytokine, chemokine receptor and ligand genes previously associated with susceptibility to cancer and autoimmune disorders as well as to infectious diseases outcome. The SNPs were displayed in two separate panels (panel 1-IL2 rs2069762, TNFα rs1800629, rs361525; IL4 rs2243250; IL6 rs1800795; IL10 rs1800896, rs1800872; IL17A rs8193036, rs2275913 and panel 2-CCR3 rs309125, CCR4 rs6770096, rs2228428; CCR6 rs968334; CCR8 rs2853699; CXCR3 rs34334103, rs2280964;CXCR6 rs223435, rs2234358; CCL20 rs13034664, rs6749704; CCL22 rs4359426; CXCL10/IP-10 rs3921, rs56061981)...
April 4, 2017: International Journal of Immunogenetics
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