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https://www.readbyqxmd.com/read/28553015/interluekin-35-in-asthma-and-its-potential-as-an-effective-therapeutic-agent
#1
REVIEW
Peng Gao, Zhenzhong Su, Xuejiao Lv, Jie Zhang
Interleukin- (IL-) 35 is a member of the IL-12 cytokine family and a heterodimeric protein formed by Epstein-Barr-induced gene 3 (EBI3) and IL-12p35. Emerging evidence shows that IL-35 is a key player in the regulation of cellular communication, differentiation, and inflammation. Altered IL-35 expression has been found in disease conditions such as cancer, rheumatoid arthritis, and, more recently, asthma. In cancer, IL-35 is involved in the regulation of tumorigenesis, cancer progression, and metastasis. In rheumatoid arthritis, IL-35 acts as a negative regulator of inflammation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28506283/prolactin-blocks-the-expression-of-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-and-reduces-osteoclastogenesis-and-bone-loss-in-murine-inflammatory-arthritis
#2
Maria G Ledesma-Colunga, Norma Adán, Georgina Ortiz, Mariana Solís-Gutiérrez, Fernando López-Barrera, Gonzalo Martínez de la Escalera, Carmen Clapp
BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28362822/fasciola-hepatica-reinfection-potentiates-a-mixed-th1-th2-th17-treg-response-and-correlates-with-the-clinical-phenotypes-of-anemia
#3
M Adela Valero, Ignacio Perez-Crespo, Carlos Chillón-Marinas, Messaoud Khoubbane, Carla Quesada, Marta Reguera-Gomez, Santiago Mas-Coma, Manuel Fresno, Núria Gironès
BACKGROUND: Fascioliasis is a severe zoonotic disease of worldwide extension caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm and anemia is the main sign. Herein, the profile of the Th1/Th2/Th17/Treg expression levels is analyzed after reinfection, correlating them with their corresponding hematological biomarkers of morbidity. METHODOLOGY/PRINCIPAL FINDINGS: The experimental design reproduces the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 8 weeks (R8), and at 12 weeks (R12), and negative control rats...
2017: PloS One
https://www.readbyqxmd.com/read/28351328/effect-of-ebi3-on-radiation-induced-immunosuppression-of-cervical-cancer-hela-cells-by-regulating-treg-cells-through-pd-1-pd-l1-pathway
#4
Song-An Zhang, Hu-Er-Xi-Dan Niyazi, Wen Hong, Gu-Li-Xian Tuluwengjiang, Lei Zhang, Yang Zhang, Wei-Peng Su, Yong-Xing Bao
This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28321150/interleukin-35-polymorphisms-are-associated-with-decreased-risk-of-premature-coronary-artery-disease-metabolic-parameters-and-il-35-levels-the-genetics-of-atherosclerotic-disease-gea-study
#5
Rosalinda Posadas-Sánchez, Nonanzit Pérez-Hernández, Javier Angeles-Martínez, Fabiola López-Bautista, Teresa Villarreal-Molina, José Manuel Rodríguez-Pérez, José Manuel Fragoso, Carlos Posadas-Romero, Gilberto Vargas-Alarcón
Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis. The aim of the present study was to establish if the polymorphisms of IL-12A and EBI3 genes that encode the IL-35 subunits are associated with the development of premature coronary artery disease (CAD) in Mexican individuals. The IL-12A and EBI3 polymorphisms were determined in 1162 patients with premature CAD and 873 controls. Under different models, the EBI3 rs428253 (OR = 0.831, Padd = 0.036; OR = 0.614, Prec = 0...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28255204/dual-roles-of-il-27-in-cancer-biology-and-immunotherapy
#6
REVIEW
Marina Fabbi, Grazia Carbotti, Silvano Ferrini
IL-27 is a pleiotropic two-chain cytokine, composed of EBI3 and IL-27p28 subunits, which is structurally related to both IL-12 and IL-6 cytokine families. IL-27 acts through a heterodimer receptor consisting of IL-27Rα (WSX1) and gp130 chains, which mediate signaling predominantly through STAT1 and STAT3. IL-27 was initially reported as an immune-enhancing cytokine that supports CD4(+) T cell proliferation, T helper (Th)1 cell differentiation, and IFN-γ production, acting in concert with IL-12. However, subsequent studies demonstrated that IL-27 displays complex immune-regulatory functions, which may result in either proinflammatory or anti-inflammatory effects in relationship to the biological context and experimental models considered...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28143936/ebi3-regulates-the-nk-cell-response-to-mouse-cytomegalovirus-infection
#7
Helle Jensen, Shih-Yu Chen, Lasse Folkersen, Garry P Nolan, Lewis L Lanier
Natural killer (NK) cells are key mediators in the control of cytomegalovirus infection. Here, we show that Epstein-Barr virus-induced 3 (EBI3) is expressed by human NK cells after NKG2D or IL-12 plus IL-18 stimulation and by mouse NK cells during mouse cytomegalovirus (MCMV) infection. The induction of EBI3 protein expression in mouse NK cells is a late activation event. Thus, early activation events of NK cells, such as IFNγ production and CD69 expression, were not affected in EBI3-deficient (Ebi3(-/-) ) C57BL/6 (B6) mice during MCMV infection...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#8
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28042143/mesenchymal-stem-cells-ameliorate-b-cell-mediated-immune-responses-and-increase-il-10-expressing-regulatory-b-cells-in-an-ebi3-dependent-manner
#9
Kyung-Ah Cho, Jun-Kyu Lee, Yu-Hee Kim, Minhwa Park, So-Youn Woo, Kyung-Ha Ryu
Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells, producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue. Conversely, IL-10-producing regulatory B (Breg) cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease. Thus, regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease...
January 2, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27983725/a-gene-expression-inflammatory-signature-specifically-predicts-multiple-myeloma-evolution-and-patients-survival
#10
C Botta, M T Di Martino, D Ciliberto, M Cucè, P Correale, M Rossi, P Tagliaferri, P Tassone
Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution...
December 16, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27919501/soluble-serum-vcam-1-whole-blood-mrna-expression-and-treatment-response-in-natalizumab-treated-multiple-sclerosis
#11
E R Petersen, H B Søndergaard, A B Oturai, Peh Jensen, P S Sorensen, F Sellebjerg, L Börnsen
BACKGROUND: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. OBJECTIVE: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27881708/il-35-suppresses-lipopolysaccharide-induced-airway-eosinophilia-in-ebi3-deficient-mice
#12
Kyosuke Kanai, Ah-Mee Park, Hiroki Yoshida, Ikuo Tsunoda, Osamu Yoshie
EBI3 functions as the subunit of immune-regulatory cytokines, such as IL-27 and IL-35, by pairing with p28 and p35, respectively. We treated wild-type and EBI3-deficient mice with intratracheal administration of LPS and obtained bronchoalveolar lavage fluid (BALF) 24 h later. Although neutrophils were the predominant cells in BALF from both groups of mice, eosinophils were highly enriched and there was increased production of eosinophil-attracting chemokines CCL11 and CCL24 in BALF of EBI3-deficient mice. The bronchial epithelial cells and alveolar macrophages were the major producers of CCL11 and CCL24...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27867385/expanding-diversity-in-molecular-structures-and-functions-of-the-il-6-il-12-heterodimeric-cytokine-family
#13
REVIEW
Hideaki Hasegawa, Izuru Mizoguchi, Yukino Chiba, Mio Ohashi, Mingli Xu, Takayuki Yoshimoto
The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play critical roles in multiple immune responses. This cytokine family has very unique characteristics in that they comprise two distinct subunits forming a heterodimer and each cytokine and receptor subunit shares with each other. The members of this cytokine family are increasing; currently, there are more than six cytokines, including the tentatively named cytokines IL-Y (p28/p40), IL-12 (p35/p40), IL-23 (p19/p40), IL-27 [p28/Epstein-Barr virus-induced protein 3 (EBI3)], IL-35 (p35/EBI3), and IL-39 (p19/EBI3)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27734415/the-immunobiology-of-interleukin-35-and-its-regulation-and-gene-expression
#14
Mei Song, Xiaojing Ma
Interleukin-35 (IL-35) is the latest addition to the IL-12 family of heterodimeric cytokines, consisting of IL-12 p35 subunit and IL-27β subunit Epstein-Barr virus induced 3 (EBI3). Since its discovery, IL-35 has been shown to exhibit immunosuppressive activities which are distinct from other members of IL-12 family. IL-35 is also unique in that it is expressed primarily by regulatory T-cells (Tregs) rather than by antigen-presenting cells (APCs). IL-35 can directly suppress effector T-cell proliferation and function and inhibit the differentiation of Th17 cells...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27682874/elevated-level-of-interleukin-35-in-colorectal-cancer-induces-conversion-of-t-cells-into-itr35-by-activating-stat1-stat3
#15
Yanhui Ma, Lei Chen, Guohua Xie, Yunlan Zhou, Chaoyan Yue, Xiangliang Yuan, Yingxia Zheng, Weiwei Wang, Lin Deng, Lisong Shen
IL-35 is a novel heterodimeric and inhibitory cytokine, composed of interleukin-12 subunit alpha (P35) and Epstein-Barr virus -induced gene 3 (EBI3). IL-35 has been reported to be produced by a range of cell types, especially regulatory T cells, and to exert immunosuppressive effects via the STATx signaling pathway. In this study, we demonstrated that IL-35 expression was elevated in both serum and tumors in patients with colorectal cancer. IL-35 mainly expressed in CD4+ T cells in human colorectal cancer tumors and adjacent tissues...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27564404/an-il-27-stat3-axis-induces-expression-of-programmed-cell-death-1-ligands-pd-l1-2-on-infiltrating-macrophages-in-lymphoma
#16
Hasita Horlad, Chaoya Ma, Hiromu Yano, Cheng Pan, Koji Ohnishi, Yukio Fujiwara, Shinya Endo, Yoshitaka Kikukawa, Yutaka Okuno, Masao Matsuoka, Motohiro Takeya, Yoshihiro Komohara
Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domaincontaining molecule-3. In the present study, we investigated the expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin-embedded tissue samples, and subsequently studied the detailed mechanism of upregulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines...
November 2016: Cancer Science
https://www.readbyqxmd.com/read/27500263/kinetics-of-alloantigen-specific-regulatory-cd4-t-cell-development-and-tissue-distribution-after-donor-specific-transfusion-and-costimulatory-blockade
#17
Yusuke Tomita, Miwa Satomi, William Bracamonte-Baran, Ewa Jankowska Gan, Andrea Szymczak Workman, Creg J Workman, Dario Angelo Alberto Vignali, William J Burlingham
BACKGROUND: The influence of donor-side regulation toward recipient antigens on graft outcome is poorly understood. METHODS: Because this influence might be due in part to the accumulation of tissue-resident memory T cells in the donor organ, we used a standard murine tolerization model (donor-specific transfusion plus CD40L blockade) to determine the kinetics of development and peripheralization of allospecific regulatory T cell in lymphoid tissues and liver, a secondary lymphoid organ used in transplantation...
May 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27492538/enhanced-lps-induced-activation-of-il-27-signalling-in-sarcoidosis
#18
Sabine Ringkowski, Joshua Loke, Shuying Huang, Hasib Ahmadzai, Felix J F Herth, Paul S Thomas, Cristan Herbert
RATIONALE: Granulomas in sarcoidosis have recently been described as containing Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits were hypothesised to differ between patients with sarcoidosis compared to healthy controls in peripheral blood. METHODS: Using a cross-sectional study design, plasma and peripheral blood mononuclear cells (PBMC) were collected from patients and control subjects...
August 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27449853/il-27-a-potential-biomarker-for-responders-to-glatiramer-acetate-therapy
#19
John E Mindur, Reuben M Valenzuela, Sudhir K Yadav, Sridhar Boppana, Suhayl Dhib-Jalbut, Kouichi Ito
Glatiramer acetate (GA) is an FDA-approved efficacious drug for the treatment of relapsing-remitting multiple sclerosis (RRMS). However, this treatment is not effective for all RRMS patients. Therefore, it is important to identify reliable biomarkers that can predict a beneficial clinical response to GA therapy. Since an increase in IL-27 has been demonstrated to suppress autoimmune and allergic diseases of inflammatory origin, we examined the effect of GA on the production of IL-27. We observed that IL-27 production in PBMCs cultured with GA was heterogeneous amongst MS patients and healthy donors (HD), and thus, defined these MS patients as either efficient, weak, or non-IL-27 producers...
July 17, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27400195/interleukin-il-39-il-23p19-epstein-barr-virus-induced-3-ebi3-induces-differentiation-expansion-of-neutrophils-in-lupus-prone-mice
#20
X Wang, X Liu, Y Zhang, Z Wang, G Zhu, G Han, G Chen, C Hou, T Wang, N Ma, B Shen, Y Li, H Xiao, R Wang
Interleukin (IL)-12 family cytokines play critical roles in autoimmune diseases. Our previous study has shown that IL-23p19 and Epstein-Barr virus-induced 3 (Ebi3) form a new IL-12 family heterodimer, IL-23p19/Ebi3, termed IL-39, and knock-down of p19 or Ebi3 reduced diseases by transferred GL7(+) B cells in lupus-prone mice. In the present study, we explore further the possible effect of IL-39 on murine lupus. We found that IL-39 in vitro and in vivo induces differentiation and/or expansion of neutrophils...
November 2016: Clinical and Experimental Immunology
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