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Gustav Arvidsson, Johan Henriksson, Birgitta Sander, Anthony P Wright
A subset of hematological cancer patients is refractory to treatment or suffers relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Using RNA sequencing and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma cells stably adhered to mouse MS-5 stromal cells or in suspension within a co-culture or cultured separately as well as in stromal cells in co-culture or in separate culture...
February 15, 2018: Haematologica
Lloyd Bod, Laetitia Douguet, Cédric Auffray, Renée Lengagne, Fériel Bekkat, Elena Rondeau, Valérie Molinier-Frenkel, Flavia Castellano, Yolande Richard, Armelle Prévost-Blondel
Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4-induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Flavia Castellano, Valérie Molinier-Frenkel
l-amino acid oxidases are flavin adenine dinucleotide-dependent enzymes present in all major kingdom of life, from bacteria to mammals. They participate in defense mechanisms by limiting the growth of most bacteria and parasites. A few mammalian LAAOs have been described, of which the enzyme "interleukin-4 induced gene 1" (IL4I1) is the best characterized. IL4I1 mainly oxidizes l-phenylalanine. It is a secreted enzyme physiologically produced by antigen presenting cells of the myeloid and B cell lineages and T helper type (Th) 17 cells...
December 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xuming Hu, Shihao Chen, Chongxin Jia, Songlei Xue, Chunfeng Dou, Zhenqing Dai, Hui Xu, Zhen Sun, Tuoyu Geng, Hengmi Cui
Avian leukosis virus J (ALVJ) infection induces hematopoietic malignancy in myeloid leukemia and hemangioma in chickens. However, little is known about the mechanisms underpinning the unique pathogenesis of ALVJ. In this study, we investigated the gene expression profiles of ALVJ-infected chicken cells and performed a comprehensive analysis of the long non-coding RNAs (lncRNAs) in CEF cells using RNA-Seq. As a result, 36 differentially expressed lncRNAs and 91 genes (FC > 2 and q-values < 0.05) were identified...
March 2018: Archives of Virology
Pegah Seddigh, Thilo Bracht, Válerie Molinier-Frenkel, Flavia Castellano, Olaf Kniemeyer, Marc Schuster, Juliane Weski, Anja Hasenberg, Andreas Kraus, Gernot Poschet, Thomas Hager, Dirk Theegarten, Christiane A Opitz, Axel A Brakhage, Barbara Sitek, Mike Hasenberg, Matthias Gunzer
The ubiquitous mold Aspergillus fumigatus threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. A. fumigatus conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during A. fumigatus infection via in vitro experiments using cell lines. We established a negative isolation protocol yielding untouched primary murine AEC II with a purity >90%, allowing ex vivo analyses of the cells, which encountered the mold in vivo By label-free proteome analysis of AEC II isolated from mice 24h after A...
December 2017: Molecular & Cellular Proteomics: MCP
Aude Aubatin, Nouhoum Sako, Xavier Decrouy, Emmanuel Donnadieu, Valérie Molinier-Frenkel, Flavia Castellano
Amino-acid catabolizing enzymes produced by mononuclear phagocytes play a central role in regulating the immune response. The mammalian phenylalanine-catabolizing enzyme IL4-induced gene 1 (IL4I1) inhibits effector T lymphocyte proliferation and facilitates regulatory T-cell development. IL4I1 expression by macrophages of various human tumors may affect patient prognosis as it facilitates tumor escape from the T-cell response in murine models. Its enzymatic activity appears to participate in its effects, but some actions of IL4I1 remain unclear...
September 10, 2017: European Journal of Immunology
Liina Pappa, Mart Kals, Paula Ann Kivistik, Andres Metspalu, Ann Paal, Tiit Nikopensius
INTRODUCTION: Neural tube defects (NTDs) are a group of common and severe congenital birth defects that occur during early embryonic development due to incomplete closure of the neural tube. The genetic architecture of human NTDs, including spina bifida and hydrocephalus, is highly heterogeneous, with multiple genes/loci and both gene-gene and gene-environment interactions involved. Hence, the variation in outcomes also most likely relates to a combination of the severity of different variants in multiple genes and genetic modifiers affecting the biochemical traits...
September 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Lloyd Bod, Renée Lengagne, Ludovic Wrobel, Jan Philipp Ramspott, Masashi Kato, Marie-Françoise Avril, Flavia Castellano, Valérie Molinier-Frenkel, Armelle Prévost-Blondel
Amino acid catabolizing enzymes emerged as a crucial mechanism used by tumors to dampen immune responses. The L-phenylalanine oxidase IL-4 induced gene 1 (IL4I1) is expressed by tumor-associated myeloid cells of most solid tumors, including melanoma. We previously provided the only evidence that IL4I1 accelerates tumor growth by limiting the CD8(+) T cell mediated immune response, in a mouse model of melanoma cell transplantation. Here, we explored the role of IL4I1 in Ret mice, a spontaneous model of melanoma...
2017: Oncoimmunology
Amber Kerstetter-Fogle
No abstract text is available yet for this article.
March 2017: Regenerative Medicine
A Arpón, J I Riezu-Boj, F I Milagro, A Marti, C Razquin, M A Martínez-González, D Corella, R Estruch, R Casas, M Fitó, E Ros, J Salas-Salvadó, J A Martínez
Epigenetic processes, including DNA methylation, might be modulated by environmental factors such as the diet, which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events. Meanwhile, Mediterranean diet (MedDiet) has demonstrated favourable effects on cardiovascular risk, blood pressure, inflammation and other complications related to excessive adiposity. Some of these effects could be mediated by epigenetic modifications. Therefore, the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells...
August 2016: Journal of Physiology and Biochemistry
Stefano Pluchino, Luca Peruzzotti-Jametti
No abstract text is available yet for this article.
December 2016: Brain: a Journal of Neurology
Konstantina Psachoulia, Kelly A Chamberlain, Dongeun Heo, Stephanie E Davis, Jeremiah D Paskus, Sonia E Nanescu, Jeffrey L Dupree, Thomas A Wynn, Jeffrey K Huang
SEE PLUCHINO AND PERUZZOTTI-JAMETTI DOI101093/AWW266 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Myelin regeneration (remyelination) is a spontaneous process that occurs following central nervous system demyelination. However, for reasons that remain poorly understood, remyelination fails in the progressive phase of multiple sclerosis. Emerging evidence indicates that alternatively activated macrophages in central nervous system lesions are required for oligodendrocyte progenitor differentiation into remyelinating oligodendrocytes...
December 2016: Brain: a Journal of Neurology
Sergio Romagnani
The interleukin (IL)-4-induced gene1 (IL4I1), which encodes the L-amino acid oxidase enzyme, plays an important immunoregulatory role. Indeed, this enzyme which is produced by B cells-including neoplastic B cells-dendritic cells and macrophages has been shown to inhibit proliferation, cytotoxicity and IFN-γ production by tumor-infiltrating CD8+ T cells, thus favoring tumor escape. Moreover, the same gene has been found to be constitutively expressed by CD4+ T helper 17 (Th17) cells, where it down-regulates cell proliferation through a reduction of CD3 chains expression in the T-cell receptor complex, thus impairing IL-2 production, and by maintaining in the same cells a high expression of Tob1, which inhibits cell cycle entry, through a still unknown mechanism...
October 2016: European Journal of Immunology
Jie Dong, Qiang Ma
Pulmonary exposure to certain forms of carbon nanotubes (CNT) induces fibrosing lesions in the lungs that manifest an acute inflammation followed by chronic interstitial fibrosis. The mechanism of CNT-induced fibrogenesis is largely unknown. The biphasic development with drastically distinct pathologic manifestations suggests a junction of acute-to-chronic transition. Here we analyzed the molecular pathways and regulators underlying the pathologic development of CNT-induced lung fibrosis. Mice were exposed to multi-walled CNT (MWCNT; XNRI MWNT-7, Mitsui; 40 μg) by pharyngeal aspiration for 7 days along with vehicle and carbonaceous controls...
September 2016: Archives of Toxicology
Wenwen Yan, Haoming Song, Jinfa Jiang, Wenjun Xu, Zhu Gong, Qianglin Duan, Chuangrong Li, Yuan Xie, Lemin Wang
The current study aimed to identify differentially expressed B cell‑associated genes in peripheral blood mononuclear cells and observe the changes in B cell activation at different stages of coronary artery disease. Groups of patients with acute myocardial infarction (AMI) and stable angina (SA), as well as healthy volunteers, were recruited into the study (n=20 per group). Whole human genome microarray analysis was performed to examine the expression of B cell‑associated genes among these three groups...
May 2016: Molecular Medicine Reports
Yinpu Yue, Wei Huang, Jingjing Liang, Jing Guo, Jian Ji, Yunliang Yao, Mingzhu Zheng, Zhijian Cai, Linrong Lu, Jianli Wang
Interleukin 4-induced gene-1 (IL4I1) was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ) expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM) differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns...
2015: PloS One
Stéphane Kerbrat, Benoit Vingert, Marie-Pierre Junier, Flavia Castellano, François Renault-Mihara, Silvina Dos Reis Tavares, Mathieu Surenaud, France Noizat-Pirenne, Jorge Boczkowski, Georges Guellaën, Hervé Chneiweiss, Sabine Le Gouvello
TCR-dependent and costimulation signaling, cell division, and cytokine environment are major factors driving cytokines expression induced by CD4(+) T cell activation. PEA-15 15 (Protein Enriched in Astrocyte / 15 kDa) is an adaptor protein that regulates death receptor-induced apoptosis and proliferation signaling by binding to FADD and relocating ERK1/2 to the cytosol, respectively. By using PEA-15-deficient mice, we examined the role of PEA-15 in TCR-dependent cytokine production in CD4(+) T cells. TCR-stimulated PEA-15-deficient CD4(+) T cells exhibited defective progression through the cell cycle associated with impaired expression of cyclin E and phosphoRb, two ERK1/2-dependent proteins of the cell cycle...
2015: PloS One
Lei Zhang, Peng Li, Ranran Liu, Maiqing Zheng, Yan Sun, Dan Wu, Yaodong Hu, Jie Wen, Guiping Zhao
The genetic improvement of disease resistance in poultry continues to be a challenge. To identify candidate genes and loci responsible for these traits, genome-wide association studies using the chicken 60k high density single nucleotide polymorphism (SNP) array for six immune traits, total serum immunoglobulin Y (IgY) level, numbers of, and the ratio of heterophils and lymphocytes, and antibody responses against Avian Influenza Virus (AIV) and Sheep Red Blood Cell (SRBC), were performed. RT-qPCR was used to quantify the relative expression of the identified candidate genes...
2015: PloS One
Céline Cousin, Aude Aubatin, Sabine Le Gouvello, Lionel Apetoh, Flavia Castellano, Valérie Molinier-Frenkel
IL4I1 (interleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converts phenylalanine (Phe) to phenylpyruvate, hydrogen peroxide, and ammonia. We have previously shown that IL4I1 is highly expressed by tumor-associated macrophages from various human cancers and facilitates immune evasion from the cytotoxic response in a murine tumor model. Indeed, IL4I1 inhibits T-cell proliferation via hydrogen peroxide toxicity on effector/memory T cells. Here, we explored the effect of IL4I1 on naïve CD4(+) T-cell differentiation...
June 2015: European Journal of Immunology
B Houston, B Curry, R J Aitken
Reactive oxygen species (ROS) are known to play an important role in the regulation of human sperm function. In this study, we demonstrate for the first time that human spermatozoa possess interleukin-induced gene 1 (IL4I1), an l-amino acid oxidase (LAAO) which is capable of generating ROS on exposure to aromatic amino acids in the presence of oxygen. The preferred substrates were found to be phenylalanine and tryptophan while the enzyme was located in the acrosomal region and midpiece of these cells. In contrast to equine and bovine spermatozoa, enzyme activity was lost as soon as the spermatozoa became non-viable...
June 2015: Reproduction: the Official Journal of the Society for the Study of Fertility
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