Adenine suppresses IgE-mediated mast cell activation
| Autor: | Seong Wook Kang, Suk-Jin Koo, Jin Bong Park, Keuna Shin, Seung-Kiel Park, Prashanta Silwal, Hyang-Joo Lee, Kun-Hoe Chung, Uk Namgung, Kyu Lim, Jun Young Heo, Jong-Il Park, Seulgi Choi |
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| Rok vydání: | 2014 |
| Předmět: |
Cell Degranulation
Immunology Immunoglobulin E Leukotriene B4 Proinflammatory cytokine Cell Line Mice Adenosine Triphosphate medicine Animals Humans Syk Kinase Mast Cells Molecular Biology Anaphylaxis Adaptor Proteins Signal Transducing Mice Inbred BALB C biology Dose-Response Relationship Drug Chemistry Kinase Phospholipase C gamma Receptors IgE Tumor Necrosis Factor-alpha Adenine Degranulation Intracellular Signaling Peptides and Proteins Protein-Tyrosine Kinases Mast cell Phosphoproteins Adenosine Molecular biology medicine.anatomical_structure Biochemistry biology.protein Tumor necrosis factor alpha Interleukin-4 Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Molecular immunology. 65(2) |
| ISSN: | 1872-9142 |
| Popis: | Nucleobase adenine is produced by dividing human lymphoblasts mainly from polyamine synthesis and inhibits immunological functions of lymphocytes. We investigated the anti-allergic effect of adenine on IgE-mediated mast cell activation in vitro and passive cutaneous anaphylaxis (PCA) in mice. Intraperitoneal injection of adenine to IgE-sensitized mice attenuated IgE-mediated PCA reaction in a dose dependent manner, resulting in a median effective concentration of 4.21 mg/kg. In mast cell cultures, only adenine among cytosine, adenine, adenosine, ADP and ATP dose-dependently suppressed FcɛRI (a high affinity receptor for IgE)-mediated degranulation with a median inhibitory concentration of 1.6mM. It also blocked the production of LTB4, an inflammatory lipid mediator, and inflammatory cytokines TNF-α and IL-4. In addition, adenine blocked thapsigargin-induced degranulation which is FcɛRI-independent but shares FcɛRI-dependent signaling events. Adenine inhibited the phosphorylation of signaling molecules important to FcɛRI-mediated allergic reactions such as Syk, PLCγ2, Gab2, Akt, and mitogen activated protein kinases ERK and JNK. From this result, we report for the first time that adenine inhibits PCA in mice and allergic reaction by inhibiting FcɛRI-mediated signaling events in mast cells. Therefore, adenine may be useful for the treatment of mast cell-mediated allergic diseases. Also, the upregulation of adenine production may provide another mechanism for suppressing mast cell activity especially at inflammatory sites. |
| Databáze: | OpenAIRE |
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