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https://www.readbyqxmd.com/read/29791566/cytidine-phosphate-guanosine-oligodeoxynucleotides-in-combination-with-cd40-ligand-decrease-periodontal-inflammation-and-alveolar-bone-loss-in-a-tlr9-independent-manner
#1
Qian Zhao, Yang Hu, Shu Deng, Pei Yu, Bowen Chen, Zuomin Wang, Xiaozhe Han
Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. OBJECTIVE: This study aimed to explore whether such effect is dependent on TLR9 signaling. MATERIAL AND METHODS: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses...
2018: Journal of Applied Oral Science: Revista FOB
https://www.readbyqxmd.com/read/29780795/a-novel-de-novo-mutation-in-the-cd40-ligand-gene-in-a-patient-with-a-mild-x-linked-hyper-igm-phenotype-initially-diagnosed-as-cvid-new-aspects-of-old-diseases
#2
Tábata T França, Luiz F B Leite, Tiago A Maximo, Christiane G Lambert, Nuria B Zurro, Wilma C N Forte, Antonio Condino-Neto
Mutations in the CD40 ligand (CD40L) gene ( CD40LG ) lead to X-linked hyper-IgM syndrome (X-HIGM), which is a primary immunodeficiency (PID) characterized by decreased serum levels of IgG and IgA and normal or elevated IgM levels. Although most X-HIGM patients become symptomatic during the first or second year of life, during which they exhibit recurrent infections, some patients exhibit mild phenotypes, which are usually associated with hypomorphic mutations that do not abrogate protein expression or function...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29767411/mek1-2-inhibition-by-binimetinib-is-effective-as-a-single-agent-and-potentiates-the-actions-of-venetoclax-and-abt-737-under-conditions-that-mimic-the-chronic-lymphocytic-leukaemia-cll-tumour-microenvironment
#3
Kyle Crassini, Yandong Shen, William S Stevenson, Richard Christopherson, Chris Ward, Stephen P Mulligan, O Giles Best
The survival and proliferation of chronic lymphocytic leukaemia (CLL) cells is driven by multiple signalling pathways, including those mediated by the B cell, Toll-like and chemokine receptors. Many of these pathways converge on the same signalling molecules, including those involved in the Raf-1/MEK/Erk1/2-MAPK pathway. We investigated the effects of the MEK1/2 (also termed MAP2K1/2) inhibitor, binimetinib, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment. Binimetinib blocked CLL cell survival induced by stroma-conditioned media and phorbol myristylate (PMA)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29761306/low-expression-of-cd40l-in-tumor-free-lymph-node-of-oral-cavity-cancer-related-with-poor-prognosis
#4
Yoon Chan Rah, Jae-Cheul Ahn, Eun-Hui Jeon, Hyojin Kim, Jin Ho Paik, Woo-Jin Jeong, Soon-Young Kwon, Soon-Hyun Ahn
BACKGROUND: Recently, the genetic alterations associated with tumor progression and impaired host immunity against transformed cells draw increased attention. Here, we characterized the differential gene expression patterns and protein expression in tumor-free lymph node from recurrent and non-recurrent tumors to identify independent prognostic markers for oral squamous cell carcinoma (OSCC). METHODS: A cDNA microarray analysis was performed to identify the differentially expressed genes in regional tumor-free lymph nodes from OSCC patients with and without recurrence...
May 14, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29751636/design-synthesis-and-evaluation-of-novel-immunomodulatory-small-molecules-targeting-the-cd40%C3%A2-cd154-costimulatory-protein-protein-interaction
#5
Damir Bojadzic, Jinshui Chen, Oscar Alcazar, Peter Buchwald
We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29739685/b-cell-subsets-imbalance-and-reduced-expression-of-cd40-in-ataxia-telangiectasia-patients
#6
C T M Pereira, D C Bichuetti-Silva, N V F da Mota, R Salomão, M K C Brunialti, B T Costa-Carvalho
BACKGROUND: Ataxia-telangiectasia (AT) is a well-known primary immunodeficiency with recurrent sinopulmonary infections and variable abnormalities in both the humoral and cellular immune system. Dysfunctions in immunoglobulin production, reduced number of B cells, and B-cell receptor excision circles copies have been reported. We aimed to understand the immunological mechanisms involving the humoral compartment in AT patients by analysing peripheral blood B cells subsets, B-T lymphocyte cooperation through the expression of CD40 and CD40 ligand (CD40L), and cytokines involved in class-switch recombination production...
May 5, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29715163/the-role-of-soluble-cd40l-ligand-in-human-carcinogenesis
#7
Anastasios Angelou, Efstathios Antoniou, Nikolaos Garmpis, Christos Damaskos, Stamatios Theocharis, Georgios-Antonios Margonis
BACKGROUND: The role of CD40/CD40L in carcinogenesis is widely examined. The mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with neoplasia are nowadays a topic of intensive research. CD40L and sCD40L belong to the TNF superfamily and are molecules with a proinflammatory role. A variety of cells express CD40L such as the immune system cells, the endothelial cells and activated platelets. Although many medications such as statins have been shown to reduce sCD40L, it is still debated whether specific treatments targeting the CD40/CD40L system will prove to be effective against carcinogenesis in the near future...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29699851/blockade-of-adhesion-molecule-lymphocyte-function-associated-antigen-1-improves-long-term-heart-allograft-survival-in-mixed-chimeras
#8
Nina Pilat, Philipp Sabler, Christoph Klaus, Benedikt Mahr, Lukas Unger, Karin Hock, Mario Wiletel, Christoph Schwarz, Ivan Kristo, Heinz Regele, Thomas Wekerle
BACKGROUND: The mixed chimerism approach for intentional induction of donor-specific tolerance was shown to be successful in various models from mice to humans. For transplant patients, the approach would obviate the need for long-term immunosuppression and associated side effects; moreover, it would preclude the risk of late graft loss due to chronic rejection. Widespread clinical application is hindered by toxicities related to recipient pre-conditioning. Herein we aimed to investigate a clinically relevant protocol for tolerance induction to cardiac allografts, sparing CD40 blockade or T-cell depletion...
March 30, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29675019/enhanced-akt-phosphorylation-of-circulating-b-cells-in-patients-with-activated-pi3k%C3%AE-syndrome
#9
Takaki Asano, Satoshi Okada, Miyuki Tsumura, Tzu-Wen Yeh, Kanako Mitsui-Sekinaka, Yuki Tsujita, Youjiro Ichinose, Akira Shimada, Kunio Hashimoto, Taizo Wada, Kohsuke Imai, Osamu Ohara, Tomohiro Morio, Shigeaki Nonoyama, Masao Kobayashi
Activated PI3Kδ syndrome (APDS) is a primary immunodeficiency characterized by recurrent respiratory tract infections, lymphoproliferation, and defective IgG production. Heterozygous mutations in PIK3CD, PIK3R1 , or PTEN , which are related to the hyperactive phosphoinositide 3-kinase (PI3K) signaling, were recently presented to cause APDS1 or APDS2 (APDSs), or APDS-like (APDS-L) disorder. In this study, we examined the AKT phosphorylation of peripheral blood lymphocytes and monocytes in patients with APDSs and APDS-L by using flow cytometry...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670614/human-v%C3%AE-9v%C3%AE-2-t-cells-synergize-cd4-t-follicular-helper-cells-to-produce-influenza-virus-specific-antibody
#10
Qingyun Chen, Kun Wen, Aizhen Lv, Ming Liu, Ke Ni, Zheng Xiang, Yinping Liu, Wenwei Tu
Human Vγ9Vδ2-T cells recognize nonpeptidic antigens and exert effector functions against microorganisms and tumors, but little is known about their roles in humoral immune response against influenza virus infection. Herein, in the coculture of autologous human B cells, dendritic cells and/or naïve CD4 T cells, and Vγ9Vδ2-T cells, we demonstrated that Vγ9Vδ2-T cells could facilitate H9N2 influenza virus-specific IgG and IgM productions in a CD4 T cell-dependent manner. Vγ9Vδ2-T cells promoted the differentiation of CXCR5+ PD1+ CD4+ T follicular helper (Tfh) cells, CD19+ IgD- CD38++ plasma cells (PCs), and drove B cell proliferation as well as immunoglobulin class switching...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670037/expression-and-regulation-of-thymic-stromal-lymphopoietin-and-thymic-stromal-lymphopoietin-receptor-heterocomplex-in-the-innate-adaptive-immunity-of-pediatric-asthma
#11
REVIEW
Sheng-Chieh Lin, Fang-Yi Cheng, Jun-Jen Liu, Yi-Ling Ye
Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi. Viral infection, pollutants and sensitivity to aeroallergens damage the epithelium from childhood, which causes asthma. The pathogenesis of asthma includes pathways of innate stimulation by environmental microbes and irritant pathogens. Damaged epithelial cells produce thymic stromal lymphopoietin (TSLP) and stimulate myeloid dendritic cell maturation through the thymic stromal lymphopoietin receptor (TSLPR) heterocomplex...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29666424/cardiovascular-markers-of-inflammation-and-serum-lipid-levels-in-hiv-infected-patients-with-undetectable-viremia
#12
Klaudija Višković, Snježana Židovec Lepej, Ana Gorenec, Ivana Grgić, Davorka Lukas, Šime Zekan, Anja Dragobratović, Maja Trupković, Josip Begovac
Patients successfully treated for HIV infection still have an increased risk for cardiovascular morbidity and mortality, which might be related not only to traditional risks, but also to inflammation and dyslipidemia. We examined the relationship of serum lipid levels with plasma biomarkers of inflammation using a composite inflammatory burden score (IBS) based on individual (>75th percentile) measurements from the following seven markers: CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin. IBS was categorized as 0 (none of the biomarkers >75th percentile), 1, 2 and 3 or more scores...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29665926/-secretory-imbalance-between-pro-inflammatory-and-anti-inflammatory-cytokines-in-the-patients-with-immune-thrombocytopenia
#13
Ming-Jing Wang, Yong-Gang Xu, Xiao-Qing Ding, Ri-Cheng Quan, Hai-Yan Chen, Zhong-Yang Deng, Pan Zhao, Teng Fan, Shi-Rong Zhu, Xiao-Mei Hu
OBJECTIVE: To analyze the imbalance of pro-inflammatory and anti-inflammatory cytokines in the patients of immune thrombocytopenia (ITP). METHODS: Thirty-five patients with ITP were enrolled in ITP group, while 28 healthy persons were included in control group. The expressions of IL-8, IL-17A, IL-22, TNF-α, IFN-γ, IL-4, CD40, CD40L, TGF-β and IL-10 were detected by flow cytometry with aimPlex multiple immunoassay Flow. RESULTS: The expressions of pro-inflammatory factors IL-8, IL-17A, IL-22, IFN-γ and TNF-α in ITP group all were significantly higher than that in the control group (P<0...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29660084/recent-developments-in-biologic-therapies-for-the-treatment-of-patients-with-systemic-lupus-erythematosus
#14
Pedro L Carreira, David A Isenberg
SLE has a complex pathogenesis, and multiple therapeutic targets have been discovered in recent years. In spite of belimumab being approved by the US Food and Drug Administration and the widespread use of rituximab, there have been many failed attempts to treat SLE successfully using biologic agents. In this review, we consider newer biologic approaches that might offer the hope of improving the outcome of SLE patients. These include the fully humanized anti-CD20 mAbs, PEGylated anti-CD40L, IFNα inhibitors, rigerimod and immune complexes blockade...
April 5, 2018: Rheumatology
https://www.readbyqxmd.com/read/29652910/elderly-dendritic-cells-respond-to-lps-ifn-%C3%AE-and-cd40l-stimulation-despite-incomplete-maturation
#15
Joanne K Gardner, Scott M J Cornwall, Arthur W Musk, John Alvarez, Cyril D S Mamotte, Connie Jackaman, Anna K Nowak, Delia J Nelson
There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated. We examined responses of blood myeloid (m)DC1s, mDC2s, plasmacytoid (p)DCs, and monocyte-derived DCs (MoDCs) from young (21-40 years) and elderly (60-84 years) healthy human volunteers to LPS/IFN-γ or CD40L stimulation...
2018: PloS One
https://www.readbyqxmd.com/read/29608021/curcumin-enhances-the-anti-cancer-effects-of-paris-saponin-ii-in-lung-cancer-cells
#16
Shuli Man, Lili Zhang, Jingxia Cui, Li Yang, Long Ma, Wenyuan Gao
OBJECTIVES: To investigate the synergistic mechanisms of Paris Saponin II (PSII) and Curcumin (CUR) in lung cancer. MATERIALS AND METHODS: The combination changed the cellular uptake of CUR and PSII, apoptosis, cell cycle arrest and cytokine levels were analysed on different lung cancer cells. RESULTS: The combination displayed a synergistic anti-cancer effect through promoting the cellular uptake of CUR on different lung cancer cells. Hoechst H33258 staining and FACS assay indicated that the combination of PSII and CUR induced cell cycle arrest and apoptosis...
April 2, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29606863/cigarette-smoke-exposure-promotes-differentiation-of-cd4-t-cells-toward-th17-cells-by-cd40-cd40l-costimulatory-pathway-in-mice
#17
Yi Liang, Ying Shen, Liangjian Kuang, Guang Zhou, Longju Zhang, Xiaoning Zhong, Jianquan Zhang, Jifeng Liu
Purpose: This study aimed to investigate the impact of cigarette smoke exposure upon CD40-CD40L ligation between bone marrow-derived dendritic cells (BMDCs)and CD4+ T cells, and to examine the effects of cigarette smoke exposure upon differentiation of CD4+ T cells toward Th17 cells through blockade of CD40-CD40L pathway in mice. Methods: The study was processed in vivo and in vitro. In vivo, Th17 cells, CD40, interleukin (IL)-17A, and IL-27 in the lung tissues were quantified and compared between mice with and without cigarette smoke exposure...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29600486/influence-of-corticosteroid-therapy-on-il-18-and-nitric-oxide-production-during-beh%C3%A3-et-s-disease
#18
Fatmazohra Djaballah-Ider, Zineb Djeraba, Mourad Chemli, Nadjiba Dammene-Debbihe, Doulkifly Lounis, Houda Belguendouz, Yanis Medour, Samia Chaib, Chafia Touil-Boukoffa
BACKGROUND AND AIMS: Behçet's disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients. METHODS: For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess' method in naïve-active and corticosteroid-treated BD patients with different clinical manifestations...
March 29, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29593458/reactive-oxygen-species-generated-by-cd45-cells-distinct-from-leukocyte-population-in-platelet-concentrates-is-correlated-with-the-expression-and-release-of-platelet-activation-markers-during-storage
#19
Mehran Ghasemzadeh, Ehteramolsadat Hosseini, Amin Shahbaz Ghasabeh, Kamran Mousavi Hosseini
Background: Platelet stimulation with agonists is accompanied by the generation of reactive oxygen species (ROS) which promotes further platelet activation and aggregation. Considering different cell populations in platelet concentrates (PCs), this study investigates the correlation of ROS generation with the expression and release of platelet activation markers during storage. Methods: Samples obtained from 6 PCs were subjected to flow cytometry and ELISA to evaluate the expression and shedding of platelet P-selectin or CD40L during storage...
January 2018: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/29577371/role-of-t-bet-the-master-regulator-of-th1-cells-in-the-cytotoxicity-of-murine-cd4-t-cells
#20
Koji Eshima, Kana Misawa, Chihiro Ohashi, Kazuya Iwabuchi
Although CD4+ T cells are generally regarded as helper T cells, some activated CD4+ T cells exert cytotoxicity. Since CD4+ cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4+ T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to the expression of IFN-γ has been well-documented, it remains unclear if T-bet is involved in CD4+ T cell-mediated cytotoxicity. In this study, in order to investigate the ability of T-bet to confer cytolytic activity on CD4+ T cells, we introduced the T-bet gene into non-cytocidal CD4+ T cell lines and analyzed their cytolytic function...
March 25, 2018: Microbiology and Immunology
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