Activation of colo-rectal high-threshold afferent nerves by Interleukin-2 is tetrodotoxin-sensitive and upregulated in a mouse model of chronic visceral hypersensitivity
Activation of colo-rectal high-threshold afferent nerves by Interleukin-2 is tetrodotoxin-sensitive and upregulated in a mouse model of chronic visceral hypersensitivity
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DOI：
10.1111/nmo.12696
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发表时间：
2016-01-01
影响因子：
3.5
通讯作者：
Hughes, P. A.
中科院分区：
文献类型：
--
作者：
Campaniello, M. A.;Harrington, A. M.;Hughes, P. A.
背景慢性内脏痛是肠易激综合征（IBS）的一个重要特征. IBS患者通常表现出先天和适应性免疫功能的改变，这可能导致症状。已知免疫介质调节内脏感觉传入神经的活性，但焦点一直在先天免疫系统上。白细胞介素-2（IL-2）主要与适应性免疫反应，但其对健康或疾病的结肠直肠传入功能的影响是unknow. MethodsMyelperoxidase（MPO）的活性确定健康，急性三硝基苯磺酸（TNBS）结肠炎的炎症程度，并在我们的后TNBS结肠炎模型的慢性内脏高敏感性（CVH）。IL-2对高阈值结肠直肠传入神经和IL-2 R和Na（V）1.7 mRNA在结肠直肠背根神经节（DRG）神经元的表达的功能影响进行了比较健康和CVH mice.Key ResultsMPO活性增加急性结肠炎期间，但消退到健康CVH小鼠的水平。IL-2引起结肠直肠传入的直接兴奋，被河豚毒素阻断。IL-2不影响传入机械敏感性健康或CVH。然而，与对照组相比，CVH小鼠中直接对IL-2反应的传入神经比例增加（73% vs 33%; p
BackgroundChronic visceral pain is a defining feature of irritable bowel syndrome (IBS). IBS patients often show alterations in innate and adaptive immune function which may contribute to symptoms. Immune mediators are known to modulate the activity of viscero-sensory afferent nerves, but the focus has been on the innate immune system. Interleukin-2 (IL-2) is primarily associated with adaptive immune responses but its effects on colo-rectal afferent function in health or disease are unknown.MethodsMyeloperoxidase (MPO) activity determined the extent of inflammation in health, acute trinitrobenzene-sulfonic acid (TNBS) colitis, and in our post-TNBS colitis model of chronic visceral hypersensitivity (CVH). The functional effects of IL-2 on high-threshold colo-rectal afferents and the expression of IL-2R and Na(V)1.7 mRNA in colo-rectal dorsal root ganglia (DRG) neurons were compared between healthy and CVH mice.Key ResultsMPO activity was increased during acute colitis, but subsided to levels comparable to health in CVH mice. IL-2 caused direct excitation of colo-rectal afferents that was blocked by tetrodotoxin. IL-2 did not affect afferent mechanosensitivity in health or CVH. However, an increased proportion of afferents responded directly to IL-2 in CVH mice compared with controls (73% vs 33%; p