Studies on the role of ALOX15 and its products in murine experimental colitis.

ALOX15及其产物在小鼠实验性结肠炎中作用的研究。

• 批准号: 269515244
• 负责人: Professor Dr. Hartmut Kühn
• 金额: --
• 依托单位: Institut für Biochemie (CCM)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/269515244?language=en
• 关键词: Studies; role; ALOX15; its; products

Preliminary unpublished data from our laboratories show that mice with a systemic knockout of the alox15 gene (12/15-lipoxygenase deficient mice) are protected from DSS-induced colitis.The main objective of the proposed project are: (1) to understand the role of alox15 in the pathogenesis of DSS-induced colitis in mice and to validate these findings on other murine colitis models, and (2) to characterize in a cell culture model the molecular mechanisms of the effect of 12/15-lipoxygenase activity and its metabolites on the function of intestinal cells.Given that the preliminary data showing a pro-inflammatory effect of ALOX15 colitis can be confirmed, and the underlying molecular pathomechanisms be identified, selective inhibitors of ALOX15 could be potential drugs for the treatment of inflammatory bowel diseases.

我们实验室未发表的初步数据显示，系统性敲除alox 15基因的小鼠（12/15-脂氧合酶缺陷小鼠）免受DSS诱导的结肠炎的影响。拟议项目的主要目标是：（1）了解alox 15在DSS诱导的小鼠结肠炎发病机制中的作用，并在其他鼠结肠炎模型上验证这些发现，以及（2）在细胞培养模型中表征12/15-脂氧合酶活性及其代谢产物对肠细胞功能的影响的分子机制。鉴于显示ALOX 15结肠炎的促炎作用的初步数据可以被证实，并且潜在的分子病理机制可以被鉴定，ALOX 15的选择性抑制剂可能是治疗炎症性肠病的潜在药物。

项目成果

Functional characterization of naturally occurring genetic variations of the human guanine-rich RNA sequence binding factor 1 (GRSF1).

• DOI: 10.1016/j.bbagen.2017.12.008
• 发表时间: 2018-04
• 期刊: Biochimica et biophysica acta. General subjects
• 作者: S. Sofi;J. Fitzgerald;Désirée Jähn;Bernhard Dumoulin;Sabine Stehling;H. Kuhn;C. Ufer

Atopic Patients Show Increased Interleukin 4 Plasma Levels but the Degree of Elevation Is Not Sufficient to Upregulate Interleukin-4-Sensitive Genes

• DOI: 10.1159/000499431
• 发表时间: 2019-05
• 期刊: Skin Pharmacology and Physiology
• 影响因子: 2.7
• 作者: Eugenia Marbach-Breitrück;Andrea Kalledat;D. Heydeck;Sabine Stehling;J. Fluhr;T. Zuberbier;H. Kuhn

Do lipoxygenases occur in viruses?: Expression and characterization of a viral lipoxygenase-like protein did not provide evidence for the existence of functional viral lipoxygenases.

• DOI: 10.1016/j.plefa.2018.10.002
• 发表时间: 2018-11
• 期刊: Prostaglandins, leukotrienes, and essential fatty acids
• 作者: T. Gehring;D. Heydeck;Agathe Niewienda;K. Janek;H. Kuhn

Mutagenesis of Sequence Determinants of Truncated Porcine ALOX15 Induces Changes in the Reaction Specificity by Altering the Catalytic Mechanism of Initial Hydrogen Abstraction.

截短猪 ALOX15 序列决定子的诱变通过改变初始夺氢的催化机制来诱导反应特异性的变化

• DOI: 10.1002/chem.201704672
• 发表时间: 2018
• 期刊: Chemistry
• 作者: Saura P;Kaganer I;Heydeck D;Lluch JM;Kühn H;González-Lafont À
• 通讯作者: González-Lafont À