Academic literature on the topic 'Inhibiteur IL-15'
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Journal articles on the topic "Inhibiteur IL-15"
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Rosset, R., S. Douville, M. Ben Amor, and K. Walha. "L'inhibition de l'entartrage par les eaux géothermales du sud tunisien. Étude sur site." Revue des sciences de l'eau 12, no. 4 (April 12, 2005): 753–64. http://dx.doi.org/10.7202/705376ar.
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Une nappe d'eaux fossiles à grande profondeur (800 à 2 700 mètres) a été mise en exploitation dans le Sud-Tunisien pour alimenter une usine d'osmose inverse située à Gabès ayant une production de 15 000 m3 /jour, afin de lutter contre la désertification par irrigation et d'assurer le chauffage de serres pour la production de primeurs. La grande dureté (TH de l'ordre de 100 à 140 °F) de ces eaux géothermales a pour conséquence le colmatage rapide des conduites de distribution : 40 à 50 tonnes de tartre par forage, constitué essentiellement de carbonate de calcium, précipitent chaque année. Ce tartre est constitué d'aragonite comme le montrent la microscopie électronique à balayage et la diffraction des rayons X. Une technique électrochimique, la chronoélectrogravimétrie, permet d'étudier l'inhibition de l'entartrage par des composés de la famille des phosphates inorganiques, des phosphonates organiques et des polycarboxylates. La concentration efficace de chacun de ces inhibiteurs agissant par effet de seuil a été déterminée : elle est de l'ordre de 1,1 à 1,5 mg.l-1 pour l'eau du forage de EL HAMMA. Un essai sur le site de EL MANSOURA a été effectué en privilégiant un inhibiteur produit industriellement dans le Sud-Tunisien, le triphosphate de sodium. A la concentration de 1 mg.l-1 il évite l'entartrage du système de refroidissement de type cascade - piscines et des conduites de distribution.
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Henry, E. "Une expérience clinique du pramipexole chez 64 patients déprimés uni ou bipolaires suivis en ambulatoire." European Psychiatry 30, S2 (November 2015): S58. http://dx.doi.org/10.1016/j.eurpsy.2015.09.162.
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Du fait de l’analogie entre apathie et dépression [1,2], nous avons utilisé le pramipexole [3] chez 64 patients déprimés (39 patients présentant une dépression uni ou bipolaire, 25 patients présentant des troubles dysthymiques). Tous les patients, depuis trois mois au moins, prenaient un traitement par inhibiteur sélectif de la recapture de la sérotonine (ISRS) maintenu sans modification. Il s’agit d’une étude rétrospective portant sur quatre années d’utilisation du pramipexole La sévérité de la dépression a été cotée par le patient sur l’échelle de Hamilton 21 items et par l’investigateur sur l’échelle Montgomery and Asberg Depression Rating Scale (MADRS). Tous les patients ont été revus un à deux mois après l’introduction du pramipexole. La posologie du pramipexole a été de 1,4 mg par jour atteinte en 16 jours. Les critères d’amélioration ont été définis comme l’obtention d’un score inférieur à 10 sur l’échelle de Hamilton et un score inférieur à 10 sur l’échelle MADRS. Parmi les 25 patients présentant un trouble dysthymique, 3 patients ont été améliorés Parmi les 39 patients présentant une dépression uni- ou bipolaire, 35 ont été améliorés. L’amélioration chez ces 38 patients est survenue 10 à 15 jours après le début du traitement. Tous les patients améliorés présentaient une variation franche de l’humeur au cours de la journée avec moindre intensité de la souffrance en fin de journée. La médiane de suivi a été de 23 mois. Les nausées (5 patients) et la somnolence (6 patients) n’ont pas nécessité de modification dans la progression de la posologie. Deux patients ont présenté un épisode maniaque résolutif en 5 à 10 jours après l’arrêt du pramipexole, 1 patient a présenté des hallucinations visuelles résolutives 15 jours après l’arrêt du pramipexole et 1 patient a présenté un priapisme résolutif dès l’arrêt du pramipexole. Aucun cas d’addiction au pramipexole n’a été observé. Au total, le pramipexole semble être un traitement bien toléré et efficace chez les patients présentant une dépression dans le cadre d’un trouble uni ou bipolaire. Il ne semble pas avoir d’indication lors de troubles dysthymiques.
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Lemogne, C. "Une prise en charge psychologique peut-elle infléchir le risque cardiovasculaire ?" European Psychiatry 28, S2 (November 2013): 39. http://dx.doi.org/10.1016/j.eurpsy.2013.09.098.
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Après ajustement sur les facteurs de risque cardiovasculaires « classiques » (tabagisme, hypertension, hypercholestérolémie, sédentarité, diabète, etc.), la dépression est associée à un risque quasiment doublé de survenue d’un premier événement coronarien ainsi qu’à un risque augmenté de 25 à 50 % de survenue d’un accident vasculaire cérébral. Il en est de même pour les symptômes anxieux. De plus, après un premier événement coronarien, la présence de symptômes dépressifs est associée à un risque augmenté de 15 à 60 % de récidive voire de mortalité cardiovasculaire. Ce constat a conduit à la mise en place de plusieurs essais contrôlés randomisés de prévention secondaire visant à démontrer l’intérêt d’une intervention pharmacologique, psychologique ou mixte sur les symptômes dépressifs dans la prévention des récidives et de la mortalité chez les patients coronariens. Globalement, les résultats obtenus jusqu’à présent ont été plutôt décevants, en particulier en ce qui concerne les études de forte puissance statistique (SADHARD, ENRICHD, CREATE, MIND-IT). Parmi ces quatre essais, trois ont montré l’intérêt d’un traitement par inhibiteur sélectif de recapture de la sérotonine ou thérapie cognitive et comportementale sur la symptomatologie dépressive, mais sans effet préventif sur la récidive des événements coronariens et la mortalité cardiovasculaire. Ce résultat paradoxal pourrait résulter de facteurs confondants, par exemple génétiques, expliquant l’association entre dépression et risque cardiovasculaire sans lien causal direct. Toutefois, certaines pistes restent encourageantes, en particulier lorsque l’intervention cible des facteurs plus généraux que la dépression tels que la gestion du stress (p.ex. essai SUPPRIM) ou au contraire repose sur une prise en charge personnalisée de la dépression (p.ex. essai COPES).
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Xu, Bo, Ashish Bhattacharjee, Biswajit Roy, Hong-Min Xu, David Anthony, David A. Frank, Gerald M. Feldman, and Martha K. Cathcart. "Interleukin-13 Induction of 15-Lipoxygenase Gene Expression Requires p38 Mitogen-Activated Protein Kinase-Mediated Serine 727 Phosphorylation of Stat1 and Stat3." Molecular and Cellular Biology 23, no. 11 (June 1, 2003): 3918–28. http://dx.doi.org/10.1128/mcb.23.11.3918-3928.2003.
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ABSTRACT Interleukin-13 (IL-13) is a cytokine secreted by Th2 lymphocytes that is capable of inducing expression of 15-lipoxygenase (15-LO) in primary human monocytes. We recently demonstrated that induction of 15-LO requires the activation of Jak2 and Tyk2 kinases and Stats 1, 3, 5, and 6. Since IL-13-induced 15-LO expression was inhibited by H7 (a serine-threonine kinase inhibitor), we predicted that Stat serine phosphorylation may also be crucial for 15-LO expression. In this study, we present evidence indicating that IL-13-induced 15-LO mRNA expression was detectable as early as 1 h by real-time reverse transcription-PCR. We found that IL-13 induced a time-dependent serine phosphorylation of both Stat1 and Stat3, detectable at 15 min after IL-13 treatment. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) was detected in a time-dependent fashion, with peak phosphorylation at 15 min after IL-13 treatment. SB202190, a p38 MAPK-specific inhibitor, markedly inhibited IL-13-induced Stat1 and Stat3 serine phosphorylation as well as DNA binding. Furthermore, treatment of cells with Stat1 or Stat3 decoys significantly impaired IL-13-induced 15-LO expression. Taken together, our results provide the first evidence that IL-13 induces p38 MAPK phosphorylation/activation, which regulates Stat1 and Stat3 serine 727 phosphorylation. Both of these events are important steps in IL-13-induced 15-LO expression in human monocytes.
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He, Jianying, Isao Usui, Ken Ishizuka, Yukiko Kanatani, Kazuyuki Hiratani, Minoru Iwata, Agussalim Bukhari, Tetsuro Haruta, Toshiyasu Sasaoka, and Masashi Kobayashi. "Interleukin-1α Inhibits Insulin Signaling with Phosphorylating Insulin Receptor Substrate-1 on Serine Residues in 3T3-L1 Adipocytes." Molecular Endocrinology 20, no. 1 (January 1, 2006): 114–24. http://dx.doi.org/10.1210/me.2005-0107.
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Abstract Proinflammatory cytokines are recently reported to inhibit insulin signaling causing insulin resistance. IL-1α is also one of the proinflammatory cytokines; however, it has not been clarified whether IL-1α may also cause insulin resistance. Here, we investigated the effects of IL-1α treatment on insulin signaling in 3T3-L1 adipocytes. IL-1α treatment up to 4 h did not alter insulin-stimulated insulin receptor tyrosine phosphorylation, whereas tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the association with phosphatidylinositol 3-kinase were partially inhibited with the maximal inhibition in around 15 min. IRS-1 was transiently phosphorylated on some serine residues around 15 min after IL-1α stimulation, when several serine kinases, IκB kinase, c-Jun-N-terminal kinase, ERK, and p70S6K were activated. Chemical inhibitors for these kinases inhibited IL-1α-induced serine phosphorylation of IRS-1. Tyrosine phosphorylation of IRS-1 was recovered only by the IKK inhibitor or JNK inhibitor, suggesting specific involvement of these two kinases. Insulin-stimulated Akt phosphorylation and 2-deoxyglucose uptake were not inhibited only by IL-1α. Interestingly, Akt phosphorylation was synergistically inhibited by IL-1α in the presence of IL-6. Taken together, short-term IL-1α treatment transiently causes insulin resistance at IRS-1 level with its serine phosphorylation. IL-1α may suppress insulin signaling downstream of IRS-1 in the presence of other cytokines, such as IL-6.
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Ju, Wei, Meili Zhang, Jian-kang Jiang, Craig J. Thomas, Unsong Oh, Bonita R. Bryant, Jing Chen, et al. "CP-690,550, a therapeutic agent, inhibits cytokine-mediated Jak3 activation and proliferation of T cells from patients with ATL and HAM/TSP." Blood 117, no. 6 (February 10, 2011): 1938–46. http://dx.doi.org/10.1182/blood-2010-09-305425.
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Abstract The retrovirus, human T-cell–lymphotrophic virus-1 (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and the neurological disorder HTLV-I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-I–encoded protein tax constitutively activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems that in turn activate the Jak3 (Janus kinase 3)/STAT5 (signal transducers and activators of transcription 5) pathway, suggesting a therapeutic strategy that involves targeting Jak3. We evaluated the action of the Jak3 inhibitor CP-690,550 on cytokine dependent ex vivo proliferation that is characteristic of peripheral blood mononuclear cells (PBMCs) from select patients with smoldering or chronic subtypes of ATL, or from those with HAM/TSP whose PBMCs are associated with autocrine/paracrine pathways that involve the production of IL-2, IL-9, IL-15, and their receptors. CP-690,550 at 50nM inhibited the 6-day ex vivo spontaneous proliferation of PBMCs from ATL and HAM/TSP patients by 67.1% and 86.4%, respectively. Furthermore, CP-690,550 inhibited STAT5 phosphorylation in isolated ATL T cells ex vivo. Finally, in an in vivo test of biological activity, CP-690,550 treatment of mice with a CD8 T-cell IL-15–transgenic leukemia that manifests an autocrine IL-15/IL-15Rα pathway prolonged the survival duration of these tumor-bearing mice. These studies support further evaluation of the Jak3 inhibitor CP-690,550 in the treatment of select patients with HTLV-I–associated ATL and HAM/TSP.
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Yamada, Yasuaki, Kazuyuki Sugawara, Tomoko Hata, Kazuto Tsuruta, Ryozo Moriuchi, Takahiro Maeda, Sunao Atogami, et al. "Interleukin-15 (IL-15) Can Replace the IL-2 Signal in IL-2–Dependent Adult T-Cell Leukemia (ATL) Cell Lines: Expression of IL-15 Receptor α on ATL Cells." Blood 91, no. 11 (June 1, 1998): 4265–72. http://dx.doi.org/10.1182/blood.v91.11.4265.
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Abstract Interleukin-15 receptor (IL-15R) and IL-2R have the same β and γ chains, but IL-15R has a specific α chain distinct from that of IL-2Rα, which is indispensable for the high affinity binding of IL-15. In the present study, we examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL-15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold excess amount of IL-2, proliferated in response to IL-15 to the same degree as to the stimulation with IL-2, and were maintained without IL-2. The responses to 1L-15 were inhibited by the antibodies against IL-2R β or γ chains but was not by the IL-2R α chain antibody. [125I]–IL-15 exhibited a single high-affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription–coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the mRNA of IL-15R α. The cell lines also had IL-15 mRNA. Despite the presence of IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of fresh ATL cells and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also responded to IL-15. These results suggest that ATL cells have the complete form of IL-15R and respond to IL-15. Such an IL-15–dependent cell proliferation mechanism might be used in the development of ATL and for the invasion and proliferation of ATL cells in the visceral organs.
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Yamada, Yasuaki, Kazuyuki Sugawara, Tomoko Hata, Kazuto Tsuruta, Ryozo Moriuchi, Takahiro Maeda, Sunao Atogami, et al. "Interleukin-15 (IL-15) Can Replace the IL-2 Signal in IL-2–Dependent Adult T-Cell Leukemia (ATL) Cell Lines: Expression of IL-15 Receptor α on ATL Cells." Blood 91, no. 11 (June 1, 1998): 4265–72. http://dx.doi.org/10.1182/blood.v91.11.4265.411k06_4265_4272.
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Interleukin-15 receptor (IL-15R) and IL-2R have the same β and γ chains, but IL-15R has a specific α chain distinct from that of IL-2Rα, which is indispensable for the high affinity binding of IL-15. In the present study, we examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL-15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold excess amount of IL-2, proliferated in response to IL-15 to the same degree as to the stimulation with IL-2, and were maintained without IL-2. The responses to 1L-15 were inhibited by the antibodies against IL-2R β or γ chains but was not by the IL-2R α chain antibody. [125I]–IL-15 exhibited a single high-affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription–coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the mRNA of IL-15R α. The cell lines also had IL-15 mRNA. Despite the presence of IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of fresh ATL cells and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also responded to IL-15. These results suggest that ATL cells have the complete form of IL-15R and respond to IL-15. Such an IL-15–dependent cell proliferation mechanism might be used in the development of ATL and for the invasion and proliferation of ATL cells in the visceral organs.
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Badolato, Raffaele, Alessandro Negro Ponzi, Maura Millesimo, Luigi D. Notarangelo, and Tiziana Musso. "Interleukin-15 (IL-15) Induces IL-8 and Monocyte Chemotactic Protein 1 Production in Human Monocytes." Blood 90, no. 7 (October 1, 1997): 2804–9. http://dx.doi.org/10.1182/blood.v90.7.2804.
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Abstract Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the β and γ components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15–contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-γ (IFN-γ) and IL-4. IFN-γ inhibited IL-15–induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.
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Badolato, Raffaele, Alessandro Negro Ponzi, Maura Millesimo, Luigi D. Notarangelo, and Tiziana Musso. "Interleukin-15 (IL-15) Induces IL-8 and Monocyte Chemotactic Protein 1 Production in Human Monocytes." Blood 90, no. 7 (October 1, 1997): 2804–9. http://dx.doi.org/10.1182/blood.v90.7.2804.2804_2804_2809.
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Interleukin-15 (IL-15) is a recently characterized cytokine that shares many biological activities with IL-2 and interacts with the β and γ components of the IL-2 receptor. Unlike IL-2, which is secreted only by T cells, IL-15 is expressed preferentially by nonlymphoid tissues, epithelial, and fibroblast cell lines and by activated monocytes/macrophages. High concentrations of IL-15 have been shown in inflamed joints of rheumatoid arthritis patients, suggesting a role for IL-15 in inflammatory diseases where there is recruitment of leukocytes. Although monocytes have been shown to bind IL-15, its effects on these cells are not defined. In this report we show that supernatants of monocytes treated with IL-15–contained chemotactic activity for neutrophils and monocytes which was neutralized by anti-IL-8 or by anti-monocyte chemotactic protein 1 (MCP-1) antibodies, respectively. Secretion of IL-8 and MCP-1 proteins is detectable by enzyme-linked immunosorbent assay as early as 6 hours after stimulation with IL-15. Production of the two chemokines is correlated with induction by IL-15 of mRNA expression in monocytes. In addition, IL-8 and MCP-1 induction by IL-15 is differently regulated by interferon-γ (IFN-γ) and IL-4. IFN-γ inhibited IL-15–induced IL-8 secretion, but synergized with IL-15 in MCP-1 induction; whereas IL-4 inhibited both IL-8 and MCP-1 induction by IL-15. These results show that IL-15 can stimulate monocytes to produce chemokines that cause inflammatory cell accumulation. Thus, IL-15 locally produced at sites of inflammation may play a pivotal role in the regulation of the leukocyte infiltrate.
Dissertations / Theses on the topic "Inhibiteur IL-15"
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Smadja, Jimmy. "Conception, synthèse et évaluation de molécules de faible poids moléculaire inhibitrices du système interleukine (IL)-15." Thesis, Nantes Université, 2022. http://www.theses.fr/2022NANU4021.
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L'interleukine (IL)-15 est une cytokine pléiotrope structurellement proche de l'IL-2, partageant toutes deux les sous-unités des récepteurs IL-2Rβ et γc. L'IL-15 joue un rôle important dans l'immunité innée et adaptative, soutenant l'activation et la prolifération des cellules NK, NK-T et CD8+ T. En cas de dérèglement, des niveaux élevés d'IL-15 ont été détectés, entraînant des réponses immunitaires anormales et des maladies auto-immunes ou inflammatoires telles que la polyarthrite rhumatoïde ou le psoriasis. Ainsi, notre objectif est de synthétiser des petites molécules inhibitrices qui se lient spécifiquement à l'IL15 sur l'interface IL-2Rᵝ. Nous décrivons ici deux nouvelles familles d'inhibiteurs de l'IL-15. En s’appuyant sur nos précédents nos travaux, de nouvelles modifications ont été apportées à notre première série labellisée IBI. Dans un deuxième temps, nous avons réalisé un docking à partir du criblage virtuel de bibliothèques de composés sur un pharmacophore affiné basé sur des résidus spécifiques de l'IL-15, identifiés sur le site de liaison de l'IL-15 avec l'IL-2Rᵝ donnant ainsi notre deuxième famille labellisée IBIS. Ces séries de composés ont été évaluées pour leur capacité à inhiber la liaison entre l'IL-15 et son récepteur, ainsi que la cascade de signalisation en aval des cellules dépendantes de l'IL-15 et leur proliférationInterleukin (IL)-15, is a pleiotropic cytokine structurally close to IL-2, both sharing the IL-2Rβ and γc receptor subunits. IL-15 plays important roles in innate and adaptative immunity, supporting the activation and proliferation of NK, NK-T, and CD8+ T cells. In case of dysregulation, high levels of IL-15 have been detected, leading to abnormal immune responses and autoimmune or inflammatory diseases such as polyarthritis rheumatoid or psoriasis. Hence, our goal is to synthesize small molecule inhibitors that bind specifically to IL15 on the IL-2Rᵝ interface. Herein, we describe two new families of IL-15 inhibitors. Taking advantage of our previous work, extending modifications were done on our first series called IBI. On a second time, we applied a similar docking-based virtual screening of compounds libraries on a refined pharmacophore-based on IL-15 specific residues identified on the binding site of IL-15 with IL- 2R giving so our second family named IBIS. These series of compounds were evaluated for their capacity to inhibit the binding to IL-15 to its cognate receptor, as well as the down-stream signaling of IL-15-dependent cells and their proliferation
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Ching-Yi, Lin, and 林靜宜. "Combined treatment of IL-6 & IL-15 activates the activity of NK cell inhibited by tumor-derived TGF-β." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/40228940633955820461.
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碩士國立臺灣大學
獸醫學研究所
91
Lowering the expression of major histocompatibility complex (MHC) molecules is one strategy by which tumors evade host immune surveillance. Low MHC expression should activate natural killer (NK) cells, which then would kill the tumor cells. However, in many tumors, NK cell cytotoxicity is suppressed. Canine transmissible venereal tumor (CTVT), which is transmitted from dog to dog by viable tumor cells through injured mucosa or skin, has low levels of MHC molecules on the cell surface. CTVT spontaneously regresses after a 4-6 months of growth. CTVT cells secrete high concentrations of TGF-β during tumor growth. TGF-β inhibits NK cell cytotoxicity. However, CTVT undergoes regression when TGF-β concentration remains high because tumor infiltrating lymphocytes (TIL) produce large amounts of IL-6. IL-6 is a strong TGF-β antagonist and is one of the key substances that restore NK cell cytotoxicity against CTVT cells. Based on these findings, we devised and tested a new immuno-gene therapy strategy that uses both IL-6 and IL-15. IL-6 antagonized the inhibitory effect of TGF-β on NK cell cytotoxicity and IL-15 promoted NK cell activity. In a cell culture system, we evaluated the role of NK cells in tumor regression and the ability of IL-6 and IL-15 to restore TGF-β-inhibited NK cell cytotoxicity. Only the treatment using both IL-6 and IL-15 effectively relieved the inhibitory effect of TGF-β and activated NK cell cytotoxicity. The IL-6 and IL-15 only treatments did not increase, or only slightly increased, NK cell cytotoxicity. Electroporation of IL-6 and IL-15 plasmids into BALB/c mice increased the ratio of NK cells in the spleen and promoted splenocyte NK cell cytotoxicity. The IL-6 and IL-15 only treatments did not significantly change the NK cell ratio or the cytotoxicity of NK cells. However, in the IL-15 treatment, there was a slight elevation of NK cell ratio. In CB17/SCID mice, electroporation with both IL-6 and IL-15 plasmids strongly inhibited the growth and establishment of CTVT. IL-6 or IL-15 alone had no effect. In CB17/SCID mice treated with anti-asialo GM-1 antibody, which blocks NK cell function, combined electroporation with IL-6 and IL-15 was unable to suppress CTVT growth. Thus, NK cells play a key role in suppressing tumors with low MHC expression and high TGF-β secretion. Gene therapy using both IL-6 and IL-15 effectively suppressed the growth and establishment of the tumor.
Conference papers on the topic "Inhibiteur IL-15"
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Schleef, R. R., M. P. Bevilacqua, M. Sawdey, M. A. Gimbrone, and D. J. Loskutoff. "INTERLEUKIN 1 (IL-1) AND TUMOR NECROSIS FACTOR (TNF) ACTIVATION OF VASCULAR ENDOTHELIUM: EFFECTS ON PLASMINOGEN ACTIVATOR INHIBITOR (PAI-1) AND TISSUE-TYPE PLASMINOGEN ACTIVATOR (tPA)." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642864.
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The regulation of the fibrinolytic system of cultured human umbilical vein endothelial cells (ECs) by two distinct monokines (IL-1 and TNF) was investigated. Conditioned media (CM) was collected from ECs cultured for 24 h in the presence of the monokines and analyzed in quantitative immunological assays for PAI-1 activity and tPA antigen. Both monokines induced a dose-dependent increase in extracellular PAI-1 activity, with a concomitant decrease in tPA antigen. Maximal effects were achieved with either 10 U/ml IL-1 or 200 U/ml of TNF, and resulted in a 4 fold increase in PAI-1 and a 50% decrease in tPA. The kinetics of the effects of both monokines on EC PAI-1 and tPA were similar, with maximal response detected at 24 h. Cell-associated PAI-1 also increased in response to these monokines. For example, a 24 h exposure of EC to TNF (250 U/ml) or IL-1 (5 U/ml) caused a 5-fold increase in cell-associated PAI-1. Northern blot analysis using a PAI-1 cDNA probe indicated that the monokines increased the levels of two RNA species, corresponding to PAI mRNAs of approximately 3.0 and 2.2 kb in length. To determine if the increase in cel 1-associated PAI-1 reflects a storage pool of rapidly releasable PAI-1, ECs were pretreated with IL-1 for 24 h, washed and the PAI-1 activity in CM measured after 5, 15 and 60 min treatment with known secretagogues (i.e., phorbol myristate acetate, calcium ionophore A23187). Although IL-1 treated ECs released PAI-1 at a rate which was 5-fold higher than controls, this rate was not increased further by treatment with phorbol myristate acetate or ionophore. The fact that both monokines act in a similar manner strengthens the hypothesis that the local development of immune and inflammatory processes could reduce endothelial fibrinolytic activity, thus leading to the pathologic formation of intravascular thrombi.
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Carlsen, E., and H. Prydz. "ROLE OF BIOLOGICAL RESPONSE MODIFIERSIN THE REGULATION OF THROMBOPLASTIN SYNTHESIS IN MONOCYTES AND ENDOTHELIAL CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643736.
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A rabbit polyclonal antibody which was monospecific for thromboplastin (TP) apoprotein from human brain according to a number of criteria was used to screen two human placenta cDNA libraries in the expression vector Agtll, one randomly primed and one oligo-dT primed, by the method of Young and Davis. 23 positive clones expressing TP related antigen were isolated and plaque purified. DNA from the different clones was isolated and the TPcDNA inserts released by EcoRl digestion. The inserts could be classified into11 size classes ranging from approx. 300-1100 base pairs.The largest insert (1100 bp) was subcloned intothe plasmid vector pGEM-1. When the nick-translated plasmid (pTP4-l) was used as a probe to screen the phage clones by slot blot hybridization all the 23clones hybridized to the 1100 bp insert. A XgtllTP4 lysogen expressed B-galactosidase- TP4 fusion peptide upon IPTG induction as shown by immunobinging studied using two different antibodies to TP apoprotein: the rabbit antibody originally used to screen the libraries and an antibody raised in goat against human brain TP purified by affinity chromatography on a Factor Vll-antiVII-agarose column.Cytokines mediate many of the cellular interactions in the inflammatory and immune response systems and have a variety of actions. We have investigated the effect of rIL-1a/$,rIL-2, rlFNa/y and rTNFa on thromboplastin synthesis (TPL) in monocytes (M) and human umbilical vein endothelial cells (HUVEC). Recombinant IL- 1a and IL-16 both induced a dose dependent increase in TPL activity of monocyte (8-fold) and HUVEC cultures (15-fold) at 6h. The increase levelled off at interleukinconcentrations of 50-100u/ml. Recombinant IL-2 at 50u/ml induced a 5-fold rise in monocytes TPL. The effect of rIL-2 on HUVEC TPL synthesis at 6 h was smaller than on monocytes but still clearly significant at dose dependent. Recombinant IFN-Y (10 -10 u/ml) increased.TPL activity in HUVEC at 6h and 16 h in adose dependent manner, whereas no effect of rIFN-Y and IFN-a (1-10 u/ml) on M TPL was seen. When LPS (5pg/ml) was used to induce TPL synthesis, additional stimulation with rIFN-Y further enhanced HUVEC TPL activity, but decreased M TPL activity. Recombinant IFNa also decreased LPS induced TPL synthesis in M andhad no effect on HUVEC TPL. Recombinant TNFa (0.3x104u/ml) increased HUVEC TPL 7-fold at 6h. There wasno effect on M TPL synthesis. No endotoxin was detected in any of these preparations. CONCLUSIONS: Some biological response modifiers induced thromboplastin synthesis in monocytes (IL-ia, IL-13, IL-2) and in human umbilical vein endothelial cells (IL-ia, IL-18, IL-2, TNFa and IFNY). Some had no direct effect on TPL synthesis but inhibited the response to monocytes to other thromboplastin-inducing agents like LPS (IFNa and IFNY).
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Mishra, Anjali, Gregory H. Sams, Jessica Johns, Douglas P. Curphey, Laura A. Sullivan, Lauren G. Falkenberg, Heather Gibson, et al. "Abstract 2858: A novel mouse model for cutaneous T-cell lymphoma reveals a role for IL-15 and activity of a new oral HDAC inhibitor." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-2858.
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