白细胞介素33和白细胞介素4调节白细胞介素31基因的表达以及由P物质和/或免疫球蛋白E刺激的人变应性疾病实验室2肥大细胞分泌白细胞介素31。
Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E.
作者信息
Petra Anastasia I, Tsilioni Irene, Taracanova Alexandra, Katsarou-Katsari Alexandra, Theoharides Theoharis C
机构信息
Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston. Massachusetts, USA.
First Department of Dermatology, A. Syggros Hospital, Athens University Medical School, Athens, Greece.
出版信息
Allergy Asthma Proc. 2018 Mar 1;39(2):153-160. doi: 10.2500/aap.2018.38.4105.
BACKGROUND
Cytokine interleukin (IL) 31 has emerged as an important component of allergic and inflammatory diseases associated with pruritus, such as atopic dermatitis (AD) and mastocytosis. Mast cells (MC) are stimulated by allergic and nonallergic triggers, and play a critical role in such diseases by secreting histamine and tryptase as well as cytokines and chemokines. IL-33 has been reported to augment MC responses, but its effect on secretion of IL-31 is not known.
OBJECTIVES
To investigate whether IL-33 can stimulate the secretion of IL-31 from cultured human MCs and whether this response is augmented by either the neuropeptide substance P (SP) or immunoglobulin E (IgE) and anti-IgE in the absence or presence of IL-4.
METHODS
Laboratory of Allergic Diseases (LAD2) human MCs were cultured in StemProH-34 SFM medium supplemented by stem cell factor and were stimulated either with IL-33 (10 ng /mL) or SP (2 μM), or preincubated with IgE (1 μg/mL) overnight, and then stimulated with anti-IgE (1 μg/mL) for 24 hours. IL-31 gene expression was measured by quantitative polymerase chain reaction, and protein was measured by enzyme-linked immunosorbent assay.
RESULTS
IL-33 (10 ng/mL) induces IL-31 gene expression, synthesis, and secretion from LAD2 cells in the absence of degranulation, whereas SP and IgE on their own have no effect. However, the effect of IL-33 is augmented by SP (2 μM) and/or IgE and anti-IgE (1 μg/mL both) and especially their combination. Moreover, this response is significantly further increased when LAD2 cells are cultured in the presence of IL-4.
CONCLUSION
These findings provide evidence that IL-33 induced secretion of IL-31 from LAD2 MC, an action augmented by novel neuroimmune interactions that may help in the development of new treatments of allergic and inflammatory diseases, especially AD and mastocytosis.
背景
细胞因子白细胞介素（IL）-31已成为与瘙痒相关的过敏性和炎症性疾病（如特应性皮炎（AD）和肥大细胞增多症）的重要组成部分。肥大细胞（MC）受到过敏和非过敏触发因素的刺激，并通过分泌组胺、类胰蛋白酶以及细胞因子和趋化因子在这些疾病中发挥关键作用。据报道，IL-33可增强MC反应，但其对IL-31分泌的影响尚不清楚。
目的
研究IL-33是否能刺激培养的人MC分泌IL-31，以及在有无IL-4的情况下，神经肽P物质（SP）或免疫球蛋白E（IgE）及抗IgE是否会增强这种反应。
方法
将变态反应疾病实验室（LAD2）人MC在添加干细胞因子的StemProH-34 SFM培养基中培养，并用IL-33（10 ng/mL）或SP（2 μM）刺激，或用IgE（1 μg/mL）预孵育过夜，然后用抗IgE（1 μg/mL）刺激24小时。通过定量聚合酶链反应测量IL-31基因表达，并用酶联免疫吸附测定法测量蛋白质。
结果
在无脱颗粒的情况下，IL-33（10 ng/mL）可诱导LAD2细胞表达、合成和分泌IL-31，而单独的SP和IgE无此作用。然而，SP（2 μM）和/或IgE及抗IgE（均为1 μg/mL），尤其是它们的组合可增强IL-33的作用。此外，当LAD2细胞在IL-4存在的情况下培养时，这种反应会显著进一步增加。
结论
这些发现提供了证据，表明IL-33可诱导LAD2 MC分泌IL-31，一种由新型神经免疫相互作用增强的作用，这可能有助于开发过敏性和炎症性疾病（尤其是AD和肥大细胞增多症）的新疗法。
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