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CD40 Ligand

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https://www.readbyqxmd.com/read/28636654/characterization-of-human-fcrl4-positive-b-cells
#1
Michel Jourdan, Nicolas Robert, Maïlys Cren, Coraline Thibaut, Christophe Duperray, Alboukadel Kassambara, Michel Cogné, Karin Tarte, Bernard Klein, Jérôme Moreaux
FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#2
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#3
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28621946/the-acute-effects-of-fine-particulate-matter-constituents-on-blood-inflammation-and-coagulation
#4
Cong Liu, Jing Cai, Renjie Chen, Liping Qiao, Hongli Wang, Wenxi Xu, Huichu Li, Zhuohui Zhao, Haidong Kan
Limited evidence is available on the effects of various fine particulate matter (PM2.5) constituents on blood inflammation and coagulation. We examined the associations between 10 constituents and 10 circulating biomarkers in a panel of 28 urban residents with 4 repeated measurements in Shanghai, China. Based on the linear mixed-effect models, we fitted the single-constituent models, the constituent-PM2.5 joint models, and the constituent-residual models to evaluate the associations between PM2.5 constituents and 8 inflammatory biomarkers (fibrinogen, C-reactive protein, monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1b, intercellular adhesion molecule-1, P-selectin, vascular cell adhesion molecule-1) and 2 coagulation biomarkers (plasminogen activator inhibitor-1 and soluble CD40 ligand)...
June 16, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28619427/soluble-cd40-ligand-derived-from-serum-is-not-correlated-with-early-ms
#5
Hamid Zahednasab, Bahaadin Siroos, Mohammad Balood, Mohammad Sajad Emami Aleagha, Mohammad Hossein Harirchian
BACKGROUND: Soluble CD40 ligand (sCD154) is a proinflammatory and prothrombotic ligand belonging to the tumor necrosis factor family. It has been shown by a variety of studies that sCD154 is elevated in the serum of patients afflicted with system autoimmune diseases. The aim of our study was to address whether sCD154 is increased in disease affected by Multiple Sclerosis (MS). METHODS: Twenty MS patients who have been newly diagnosed as clinically definite multiple sclerosis (CDMS) along with twenty age and sex matched healthy individuals were recruited for this study...
May 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28609750/association-of-plasma-cd40l-with-acute-chest-syndrome-in-sickle-cell-anemia
#6
Vanessa Tonin Garrido, Laura Sonzogni, Siana Nkya Mtatiro, Fernando F Costa, Nicola Conran, Swee Lay Thein
Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We sought to evaluate the association of CD40L and inflammation with sickle-related clinical complications and laboratory variables in SCA patients. Soluble CD40L, thrombospondin (TSP)-1 and tumor necrosis factor (TNF)-α were determined in the platelet-poor plasma of healthy individuals and steady-state SCA patients by ELISA...
June 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28609704/sphingosine-1-phosphate-s1p-suppresses-the-collagen-induced-activation-of-human-platelets-via-s1p4-receptor
#7
Takashi Onuma, Kumiko Tanabe, Yuko Kito, Masanori Tsujimoto, Kodai Uematsu, Yukiko Enomoto, Rie Matsushima-Nishiwaki, Tomoaki Doi, Kiyoshi Nagase, Shigeru Akamatsu, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida
Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation...
June 2, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28608165/platelet-related-biomarkers-and-their-response-to-inhibition-with-aspirin-and-p2y12-receptor-antagonists-in-patients-with-acute-coronary-syndrome
#8
Angela Lowenstern, Robert F Storey, Megan Neely, Jie-Lena Sun, Dominick J Angiolillo, Christopher P Cannon, Anders Himmelmann, Kurt Huber, Stefan K James, Hugo A Katus, Joao Morais, Agneta Siegbahn, Phillippe Gabriel Steg, Lars Wallentin, Richard C Becker
The PLATelet inhibition and patient Outcomes (PLATO) trial showed that treatment with ticagrelor reduced the rate of death due to vascular causes, myocardial infarction and stroke when compared to clopidogrel in patients with ST-elevation or non-ST-elevation acute coronary syndrome (ACS). While the comparative benefit of ticagrelor over clopidogrel increased over time, event rates accrued in both groups during the study period. The purpose of our biomarker-based exploratory analysis was to determine whether long-term platelet inhibition may be associated with platelet adaptation...
June 12, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28602123/paraoxonase-1-and-myeloperoxidase-correlate-with-vascular-biomarkers-in-overweight-patients-with-newly-diagnosed-untreated-hyperlipidaemia
#9
Anita Szentpéteri, Noémi Zsíros, Viktória E Varga, Hajnalka Lőrincz, Mónika Katkó, Ildikó Seres, Péter Fülöp, György Paragh, Mariann Harangi
BACKGROUND: In hyperlipidaemic state, increased levels of myeloperoxidase (MPO) and decreased paraoxonase-1 (PON1) activity have been reported; however, their relationships with other atherosclerotic biomarkers have not been completely clarified. PATIENTS AND METHODS: Serum concentrations of lipid and inflammatory parameters, MPO levels, and PON1 activities were investigated in 167 untreated hyperlipidaemic patients with and without vascular complications and in 32 healthy controls...
June 12, 2017: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/28583714/il-21-anti-tim1-cd40-ligand-promotes-b10-activity-in-vitro-and-alleviates-bone-loss-in-experimental-periodontitis-in-vivo
#10
Yang Hu, Pei Yu, Xinbo Yu, Xingxue Hu, Toshihisa Kawai, Xiaozhe Han
IL-10-expressing regulatory B cells (B10) play an essential role in immune system balance by suppressing excessive inflammatory responses. In this study, we investigated induction of B 10 cell's IL-10 competency in vitro and its effect on ligature-induced experimental periodontitis in vivo. Spleen B cells were isolated from C57BL/6J mice and cultured for 48 hours under the following conditions: control, CD40L, IL-21, anti-Tim1, CD40L+IL-21, CD40L+anti-Tim1, CD40L+IL-21+anti-Tim1. Silk ligatures were tied around both maxillary second molars of C57BL/6J mice for two weeks...
June 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28583568/comparison-of-flow-cytometric-antibody-secreting-cell-assay-and-mabtech-immunoglobulin-elispot-assay
#11
N Lee, J W In, H Kim, E Y Roh, S Shin, K U Park, J Yang, E Y Song
BACKGROUND: The increase of donor-specific antibodies (DSA) after transplantation could be a more important marker than the level of DSA in pre-transplantation sera. The assessment of sensitized cells that can secrete DSA is needed. We developed an assay for antibody-secreting cells (ASCs) measured with the use of flow cytometry and compared it with the Mabtech immunoglobulin (IgG) ELISpot assay. METHODS: Thirteen patients who were awaiting or received organ transplantation and 15 healthy control subjects were included...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28570959/non-survivor-septic-patients-have-persistently-higher-serum-scd40l-levels-than-survivors
#12
Leonardo Lorente, María M Martín, Antonia Pérez-Cejas, José Ferreres, Jordi Solé-Violán, Lorenzo Labarta, César Díaz, Alejandro Jiménez
INTRODUCTION: Soluble CD40 ligand (sCD40L) is a protein with proinflammatory and prothrombotic effects. Previously we found higher circulating sCD40L levels in non-survivor than in survivor patients at sepsis diagnosis. Now some questions arise such as how are serum sCD40L levels during the first week of severe sepsis?, is there an association between serum sCD40L levels during the first week and mortality?, and serum sCD40L levels during the first week could be used as sepsis mortality biomarker?...
May 24, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28566713/a-ppar%C3%AE-dependent-mir-424-503-cd40-axis-regulates-inflammation-mediated-angiogenesis
#13
Aram Lee, Irinna Papangeli, Youngsook Park, Ha-Neul Jeong, Jihea Choi, Hyesoo Kang, Ha-Neul Jo, Jongmin Kim, Hyung J Chun
Activation of the endothelium by pro-inflammatory stimuli plays a key role in the pathogenesis of a multitude of vascular diseases. Angiogenesis is a crucial component of the vascular response associated with inflammatory signaling. The CD40/CD40 ligand dyad in endothelial cells (EC) has a central role in promoting vascular inflammatory response; however, the molecular mechanism underlying this component of inflammation and angiogenesis is not fully understood. Here we report a novel microRNA mediated suppression of endothelial CD40 expression...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28558009/association-between-aqueous-humor-and-vitreous-fluid-levels-of-th17-cell-related-cytokines-in-patients-with-proliferative-diabetic-retinopathy
#14
Masaru Takeuchi, Tomohito Sato, Yutaka Sakurai, Manzo Taguchi, Kozo Harimoto, Yoko Karasawa, Masataka Ito
Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28546465/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#15
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
May 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28521278/scaffold-protein-jlp-mediates-tcr-initiated-cd4-t-cell-activation-and-cd154-expression
#16
Qi Yan, Cheng Yang, Qiang Fu, Zhaowei Chen, Shan Liu, Dou Fu, Rahmat N Rahman, Ryota Nakazato, Katsuji Yoshioka, Sam K P Kung, Guohua Ding, Huiming Wang
CD4(+) T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4(+) T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4(+) T cells...
May 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28505514/tlr4-supports-the-expansion-of-fasl-cd5-cd1d-hi-regulatory-b-cells-which-decreases-in-contact-hypersensitivity
#17
Keng Wang, Lei Tao, Jianbing Su, Yueyang Zhang, Binhua Zou, Yiyuan Wang, Min Zou, Nana Chen, Linsheng Lei, Xiaojuan Li
Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5(+)CD1d(hi) Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5(+)CD1d(hi) Bregs. In this study, we isolated splenocytes or splenic CD19(+) B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5(+)CD1d(hi) Bregs by flow cytometry...
May 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28495432/changes-in-coagulation-and-platelet-activation-markers-following-transcatheter-left-atrial-appendage-closure
#18
Josep Rodés-Cabau, Gilles O'Hara, Jean-Michel Paradis, Mathieu Bernier, Tania Rodriguez-Gabella, Ander Regueiro, Kim O'Connor, Jonathan Beaudoin, Rishi Puri, Mélanie Côté, Jean Champagne
The recommendations for antithrombotic treatment after left atrial appendage closure (LAAC) remain empirical, and no data exist on the changes in hemostatic markers associated with LACC. The objective of the present study is to determine the presence, degree, and timing of changes in the markers of platelet and coagulation activation after LAAC. Forty-three patients (mean age 76 ± 9 years, 23 men) with atrial fibrillation who underwent successful LACC with the Watchman (n = 27) or Amplatzer Cardiac Plug (n = 16) devices were included in the study...
April 12, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28491094/immunoprofiling-of-adult-derived-human-liver-stem-progenitor-cells-impact-of-hepatogenic-differentiation-and-inflammation
#19
Hoda El-Kehdy, Camillo Sargiacomo, Mohammad Fayyad-Kazan, Hussein Fayyad-Kazan, Catherine Lombard, Laurence Lagneaux, Etienne Sokal, Mehdi Najar, Mustapha Najimi
Adult-derived human liver stem/progenitor cells (ADHLSCs) are, nowadays, developed as therapeutic medicinal product for the treatment of liver defects. In this study, the impact of hepatogenic differentiation and inflammation priming on the ADHLSCs' immune profile was assessed in vitro and compared to that of mature hepatocytes. The constitutive immunological profile of ADHLSCs was greatly different from that of hepatocytes. Differences in the expression of the stromal markers CD90 and CD105, adhesion molecules CD44 and CD49e, immunoregulatory molecules CD73 and HO-1, and NK ligands CD112 and CD155 were noted...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28490810/establishment-of-induced-pluripotent-stem-cells-from-normal-b-cells-and-inducing-aid-expression-in-their-differentiation-into-hematopoietic-progenitor-cells
#20
Fumihiko Kawamura, Makoto Inaki, Atsushi Katafuchi, Yu Abe, Naohiro Tsuyama, Yumiko Kurosu, Aki Yanagi, Mitsunori Higuchi, Satoshi Muto, Takumi Yamaura, Hiroyuki Suzuki, Hideyoshi Noji, Shinichi Suzuki, Mitsuaki A Yoshida, Megumi Sasatani, Kenji Kamiya, Masafumi Onodera, Akira Sakai
B cell derived induced pluripotent stem cells (BiPSCs) were recently established from peripheral blood B cells by the simultaneous transfection of Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPα using a Sendai virus vector. Here, using a different method, we established BiPSCs with immunoglobulin heavy chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The critical points of our method are pre-stimulation of B cells with IL-21 and CD40-ligand (CD40L), followed by consecutive transfection of highly concentrated Yamanaka factors using a retroviral vector...
May 10, 2017: Scientific Reports
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