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https://www.readbyqxmd.com/read/28282577/therapeutic-efficacy-of-a-co-blockade-of-il-13-and-il-25-on-airway-inflammation-and-remodeling-in-a-mouse-model-of-asthma
#1
Fang-Qi Zhang, Xin-Peng Han, Fang Zhang, Xuan Ma, Dong Xiang, Xue-Min Yang, Hai-Feng Ou-Yang, Zhikui Li
Repeated airway inflammation and unremitting remodeling provoke irreversible pulmonary dysfunction and resistance to current drugs in patients with chronic bronchial asthma. Interleukin (IL)-13 and IL-25 play an important role in airway inflammation and remodeling in asthma. We aimed to investigate whether co-inhibiting IL-13 and IL-25 can effectively down-regulate allergen-induced airway inflammation and remodeling in mice. Mice with asthma induced by chronic exposure to ovalbumin (OVA) were given soluble IL-13 receptor α2 (sIL-13R) or soluble IL-25 receptor (sIL-25R) protein alone and in combination to neutralize the bioactivity of IL-13 and IL-25, and relevant airway inflammation and remodeling experiments were performed...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28143704/-22%C3%AE-25r-3%C3%AE-hydroxy-spirost-5-en-7-iminoxy-heptanoic-acid-exhibits-anti-prostate-cancer-activity-through-caspase-pathway
#2
A A Hamid, Tanu Kaushal, Raghib Ashraf, Arjun Singh, Amit Chand Gupta, Om Prakash, Jayanta Sarkar, Debabrata Chanda, D U Bawankule, Feroz Khan, Karuna Shanker, O O Aiyelaagbe, Arvind S Negi
Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC50 ranging from 12 to 35μM. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway...
January 28, 2017: Steroids
https://www.readbyqxmd.com/read/27878760/reduced-plasma-levels-of-25-hydroxycholesterol-and-increased-cerebrospinal-fluid-levels-of-bile-acid-precursors-in-multiple-sclerosis-patients
#3
Peter J Crick, William J Griffiths, Juan Zhang, Martin Beibel, Jonas Abdel-Khalik, Jens Kuhle, Andreas W Sailer, Yuqin Wang
Multiple sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS). We have measured the levels of over 20 non-esterified sterols in plasma and cerebrospinal fluid (CSF) from patients suffering from MS, inflammatory CNS disease, neurodegenerative disease and control patients. Analysis was performed following enzyme-assisted derivatisation by liquid chromatography-mass spectrometry (LC-MS) exploiting multistage fragmentation (MS (n) ). We found increased concentrations of bile acid precursors in CSF from each of the disease states and that patients with inflammatory CNS disease classified as suspected autoimmune disease or of unknown aetiology also showed elevated concentrations of 25-hydroxycholestertol (25-HC, P < 0...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27870664/targeting-il-25-as-a-novel-therapy-in-chronic-rhinosinusitis-with-nasal-polyps
#4
Mingyu Lee, Dae Woo Kim, Hyun-Woo Shin
PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disorder with a poorly understood pathophysiology. Recent findings show that epithelial-derived cytokines, including thymic stromal lymphopoietin, IL-33, and IL-25, can exacerbate Th2 immune responses, ultimately leading to recalcitrant chronic rhinosinusitis and nasal polyps. Although IL-25 is increased in CRSwNP, the targeting of IL-25 as a therapeutic strategy remains largely unexplored...
February 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27749818/single-cell-rna-seq-identifies-a-pd-1-hi-ilc-progenitor-and-defines-its-development-pathway
#5
Yong Yu, Jason C H Tsang, Cui Wang, Simon Clare, Juexuan Wang, Xi Chen, Cordelia Brandt, Leanne Kane, Lia S Campos, Liming Lu, Gabrielle T Belz, Andrew N J McKenzie, Sarah A Teichmann, Gordon Dougan, Pentao Liu
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis. ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the α-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments. ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3)...
November 3, 2016: Nature
https://www.readbyqxmd.com/read/27685606/allergen-induced-increases-in-interleukin-25-and-interleukin-25-receptor-expression-in-mature-eosinophils-from-atopic-asthmatics
#6
Wei Tang, Steven G Smith, Brittany Salter, John Paul Oliveria, Patrick Mitchell, Graeme M Nusca, Karen Howie, Gail M Gauvreau, Paul M O'Byrne, Roma Sehmi
BACKGROUND: Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics. METHODS: Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/25821217/a-novel-il-25-signaling-pathway-through-stat5
#7
Ling Wu, Jarod A Zepp, Wen Qian, Bradley N Martin, Wenjun Ouyang, Weiguo Yin, Kevin D Bunting, Mark Aronica, Serpil Erzurum, Xiaoxia Li
IL-25 is a member of the IL-17 family of cytokines that promotes Th2 cell-mediated inflammatory responses. IL-25 signals through a heterodimeric receptor (IL-25R) composed of IL-17RA and IL-17RB, which recruits the adaptor molecule Act1 for downstream signaling. Although the role of IL-25 in potentiating type 2 inflammation is well characterized by its ability to activate the epithelium as well as T cells, the components of its signaling cascade remain largely unknown. In this study, we found that IL-25 can directly activate STAT5 independently of Act1...
May 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25676453/increased-expression-of-thymic-stromal-lymphopoietin-and-its-receptor-in-kimura-s-disease
#8
Eri Sakitani, Manabu Nonaka, Noriyuki Shibata, Toru Furukawa, Toshio Yoshihara
OBJECTIVE: The objective of this study was to investigate the expression of thymic stromal lymphopoietin (TSLP) and TSLP receptor (TSLPR) in Kimura's disease (KD). METHODS: Using parotid gland tissues from KD patients and control subjects, we quantified the expression levels of mRNA for TSLP, interleukin (IL)-25, IL-33, and their receptors by massively parallel sequencing. We also performed immunohistochemical analysis of TSLP and TSLPR, and counted cells immunoreactive for these proteins by the polymer immunocomplex and double immunofluorescence methods...
2015: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/25466271/induction-of-anti-proliferative-and-apoptotic-effects-by-anti-il-25-receptor-single-chain-antibodies-in-breast-cancer-cells
#9
Vahid Younesi, Foroogh Nejatollahi
Overexpression of IL-25 receptor (IL-25R) on the surface of malignant, but not normal, breast epithelial cells contributes to tumorigenic potential of breast cancer cells. IL-25/IL-25R binding results in specific apoptosis in breast cancer cells. In this study, the inhibitory effects of anti-IL-25R scFv antibodies on three breast cancer cells were evaluated. Panning process was performed on a phage library to isolate scFvs against two specific epitopes of IL25R. The reactivities of scFvs were assessed using phage ELISA...
December 2014: International Immunopharmacology
https://www.readbyqxmd.com/read/25015831/il-33-and-thymic-stromal-lymphopoietin-mediate-immune-pathology-in-response-to-chronic-airborne-allergen-exposure
#10
Koji Iijima, Takao Kobayashi, Kenichiro Hara, Gail M Kephart, Steven F Ziegler, Andrew N McKenzie, Hirohito Kita
Humans are frequently exposed to various airborne allergens in the atmospheric environment. These allergens may trigger a complex network of immune responses in the airways, resulting in asthma and other chronic airway diseases. In this study, we investigated the immunological mechanisms involved in the pathological changes induced by chronic exposure to multiple airborne allergens. Naive mice were exposed intranasally to a combination of common airborne allergens, including the house dust mite, Alternaria, and Aspergillus, for up to 8 wk...
August 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/24084331/identification-of-a-soluble-isoform-of-human-il-17ra-generated-by-alternative-splicing
#11
Miwa Sohda, Yoshio Misumi, Kosuke Tashiro, Manabu Yamazaki, Takashi Saku, Kimimitsu Oda
IL-17RA, a member of the interleukin (IL)-17 receptor family, is a single membrane-spanning protein that ubiquitously expressed on the cell surface. IL-17RA transduces IL-17A, IL-17F, and IL-17A/F heterodimer-mediated signals by forming a complex with IL-17RC, and also signals the IL-17E (also known as IL-25) response in combination with IL-17RB (also known as IL-25R). Previously, soluble isoforms of human IL-17RC and IL-17RB have been reported, but the existence of a soluble isoform of human IL-17RA has remained unclear...
December 2013: Cytokine
https://www.readbyqxmd.com/read/23851685/critical-role-of-p38-and-gata3-in-natural-helper-cell-function
#12
Jun-ichi Furusawa, Kazuyo Moro, Yasutaka Motomura, Kazuo Okamoto, Jinfang Zhu, Hiroshi Takayanagi, Masato Kubo, Shigeo Koyasu
Natural helper (NH) cells, a member of Lin(-)IL-2R(+)IL-7R(+)IL-25R(+)IL-33R(+)GATA3(+) group 2 innate lymphoid cell subset, are characterized by the expression of transcription factors GATA3 and RORα and production of large amounts of Th2 cytokines such as IL-5, IL-6, and IL-13 upon IL-33 stimulation or a combination of IL-2 and IL-25. We have studied the signal transduction pathways critical for the cytokine expression and development of NH cell. Either stimulation with IL-33 or a combination of IL-2 and IL-25 induced p38 activation and phosphorylation of GATA3 in NH cells, and the phosphorylated form of GATA3 bound to the IL-5 and IL-13 promoters...
August 15, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/22045852/a-cc-loop-decoy-peptide-blocks-the-interaction-between-act1-and-il-17ra-to-attenuate-il-17-and-il-25-induced-inflammation
#13
Caini Liu, Shadi Swaidani, Wen Qian, Zizhen Kang, Paige Sun, Yue Han, Chenhui Wang, Muhammet Fatih Gulen, Weiguo Yin, Chunjiang Zhang, Paul L Fox, Mark Aronica, Thomas A Hamilton, Saurav Misra, Junpeng Deng, Xiaoxia Li
Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes encoding inflammatory factors and are implicated in the pathology of various inflammatory diseases. Nuclear factor κB (NF-κB) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for signaling by either IL-17 or IL-25, and it is recruited to their receptors (IL-17R and IL-25R) through heterotypic interactions between the SEFIR [SEF (similar expression to fibroblast growth factor genes) and IL-17R] domain of Act1 and that of the receptor...
2011: Science Signaling
https://www.readbyqxmd.com/read/21570719/allergen-induced-expression-of-il-25-and-il-25-receptor-in-atopic-asthmatic-airways-and-late-phase-cutaneous-responses
#14
Chris J Corrigan, Wei Wang, Qiu Meng, Cailong Fang, Ghada Eid, M Rosario Caballero, Ze Lv, Yunqing An, Yui-Hsi Wang, Yong-Jun Liu, A Barry Kay, Tak H Lee, Sun Ying
BACKGROUND: IL-25 is thought to participate in allergic inflammation by propagating T(h)2-type responses. OBJECTIVE: To address the hypothesis that allergen provocation increases expression of IL-25 and its receptor IL-25R in the asthmatic bronchial mucosa and skin dermis of atopic subjects. METHODS: Sequential single and double immunostaining was used to evaluate the numbers and phenotypes of IL-25 and IL-25R immunoreactive cells in bronchial biopsies from mild atopic subjects with asthma (n = 10) before and 24 hours after allergen inhalation challenge and skin biopsies from atopic subjects (n = 10) up to 72 hours after allergen subepidermal injection...
July 2011: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/21490275/il-25-causes-apoptosis-of-il-25r-expressing-breast-cancer-cells-without-toxicity-to-nonmalignant-cells
#15
Saori Furuta, Yung-Ming Jeng, Longen Zhou, Lan Huang, Irene Kuhn, Mina J Bissell, Wen-Hwa Lee
As cells differentiate into tissues, the microenvironment that surrounds these cells must cooperate so that properly organized, growth-controlled tissues are developed and maintained. We asked whether substances produced from this collaboration might thwart malignant cells if they arise in the vicinity of normal tissues. Here, we identified six factors secreted by nonmalignant mammary epithelial cells (MECs) differentiating in three-dimensional laminin-rich gels that exert cytotoxic activity on breast cancer cells...
April 13, 2011: Science Translational Medicine
https://www.readbyqxmd.com/read/21205894/t-helper-cell-type-2-th2-memory-t-cell-potentiating-cytokine-il-25-has-the-potential-to-promote-angiogenesis-in-asthma
#16
Chris J Corrigan, Wei Wang, Qiu Meng, Cailong Fang, Huifen Wu, Victoria Reay, Ze Lv, Yiqiang Fan, Yunqing An, Yui-Hsi Wang, Yong-Jun Liu, Tak H Lee, Sun Ying
IL-25 (IL-17E) is a T-helper cell type 2 (Th2) cytokine best described as a potentiator of Th2 memory responses. Reports of expression of its receptor, IL-25R, on airways structural cells suggest a wider role for IL-25 in remodeling. We hypothesized that IL-25 stimulates local angiogenesis in the asthmatic bronchial mucosa. Immunoreactive IL-25(+), IL-25R(+), and CD31(+) (endothelial) cells in sections of bronchial biopsies from asthmatics and controls were detected by immunohistochemistry. The effect of IL-25 on angiogenesis was examined using an in vitro assay...
January 25, 2011: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/19828636/pulmonary-il-17e-il-25-production-and-il-17rb-myeloid-cell-derived-th2-cytokine-production-are-dependent-upon-stem-cell-factor-induced-responses-during-chronic-allergic-pulmonary-disease
#17
Vladislav Dolgachev, Bryan C Petersen, Alison L Budelsky, Aaron A Berlin, Nicholas W Lukacs
In the present studies local neutralization of allergen-induced stem cell factor (SCF) leads to decreased production of Th2 cytokines, a reduction in inflammation, allergen-specific serum IgE/IgG1, and attenuation of severe asthma-like responses. The local blockade of pulmonary SCF also resulted in a significant reduction of IL-17E (IL-25). Sorted cell populations from the lung indicated that IL-25 was produced from c-kit(+) cells, whereas Th2 cytokine production was primarily from c-kit(-) cell populations...
November 1, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/19505427/interleukin-25-inhibits-interleukin-12-production-and-th1-cell-driven-inflammation-in-the-gut
#18
COMPARATIVE STUDY
Roberta Caruso, Massimiliano Sarra, Carmine Stolfi, Angelamaria Rizzo, Daniele Fina, Massimo Claudio Fantini, Francesco Pallone, Thomas T MacDonald, Giovanni Monteleone
BACKGROUND & AIMS: During the pathogenesis of Crohn's disease (CD), interleukin (IL)-12, a cytokine produced by mucosal CD14+ monocyte-like cells, promotes tissue-damaging T helper cell (Th) 1-mediated inflammation through mechanisms that are not fully understood. IL-25 promotes Th2 cell responses by activating major histocompatibility complex class II-positive non-T and non-B cells. Because Th1 and Th2 cells, and the cytokines they release, are often mutually antagonistic, we examined whether IL-25 affects IL-12 production or Th1 cell-mediated inflammation in the gut...
June 2009: Gastroenterology
https://www.readbyqxmd.com/read/19400908/thymic-stromal-lymphopoietin-ox40-ligand-and-interleukin-25-in-allergic-responses
#19
REVIEW
Y-H Wang, Y-J Liu
Allergic diseases are often triggered by environmental allergens that induce dominant type 2 immune responses, characterized by the infiltrated T-helper type 2 (TH2) lymphocytes, eosinophils, and elevated TH2 cytokines. In addition to TH2 type immune responses, epithelial stress and injury linked to tissue remodelling are often observed, suggesting that epithelial cells may play important role in regulating allergic responses. Dendritic cells (DCs), the professional antigen-presenting cells with the capabilities of sampling allergens, are considered as the key player on instructing TH2 immune responses...
June 2009: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/19155512/the-critical-role-of-epithelial-derived-act1-in-il-17-and-il-25-mediated-pulmonary-inflammation
#20
COMPARATIVE STUDY
Shadi Swaidani, Katarzyna Bulek, Zizhen Kang, Caini Liu, Yi Lu, Weiguo Yin, Mark Aronica, Xiaoxia Li
IL-25 initiates, promotes, and augments Th2 immune responses. In this study, we report that Act1, a key component in IL-17-mediated signaling, is an essential signaling molecule for IL-25 signaling. Although Act1-deficient mice showed reduced expression of KC (CXCL1) and neutrophil recruitment to the airway compared with wild-type mice in response to IL-17 stimulation, Act1 deficiency abolished IL-25-induced expression of IL-4, IL-5, IL-13, eotaxin-1 (CCL11), and pulmonary eosinophilia. Using a mouse model of allergic pulmonary inflammation, we observed diminished Th2 responses and lung inflammation in Act1-deficient mice compared with wild-type mice...
February 1, 2009: Journal of Immunology: Official Journal of the American Association of Immunologists
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