Modulation of inflammatory response via α2-adrenoceptor blockade in acute murine colitis
Modulation of inflammatory response via α2-adrenoceptor blockade in acute murine colitis
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DOI：
10.1111/j.1365-2249.2009.03894.x
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发表时间：
2009-05-01
影响因子：
4.6
通讯作者：
Liu, Z.
中科院分区：
文献类型：
--
作者：
Bai, A.;Lu, N.;Liu, Z.
炎症性肠病（IBD）的特征在于大量产生促炎细胞因子，如肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1 β。自主神经系统与局部免疫细胞的相互作用在IBD的发生中发挥重要作用，交感神经过度活跃的IBD患者自主神经功能平衡被打破。然而，在结肠炎的进展中，儿茶酚胺的功能尚不清楚。在这项研究中，我们研究了通过α 2肾上腺素受体在急性小鼠结肠炎中的作用。采用免疫组织化学方法检测了儿茶酚胺合成限速酶酪氨酸羟化酶（TH）和多巴胺b-羟化酶（DBH）在小鼠结肠炎中的表达。用葡聚糖硫酸钠或三硝基苯磺酸（TNBS）诱导小鼠结肠炎，并给予小鼠RX 821002或UK 14304、α 2-肾上腺素受体拮抗剂或激动剂。通过临床症状、髓过氧化物酶测定、TNF-α和IL-1 β产生和组织学评价结肠炎。在不存在或存在RX 821002或UK 14304的情况下培养来自患有TNBS结肠炎的小鼠的固有层单核细胞（LPMC），并进一步通过脂多糖刺激。TH和DBH在炎症结肠的LPMC中被诱导，这是结肠炎过程中儿茶酚胺合成的证据。RX 821002下调LPMC产生促炎细胞因子，而UK 14304导致结肠炎恶化。总之，我们的数据表明，通过α 2-肾上腺素受体的急性结肠炎的进展中的关键作用，儿茶酚胺，并建议使用α 2-肾上腺素受体拮抗剂代表了一种新的治疗方法，结肠炎的管理。
Inflammatory bowel disease (IBD) is characterized by heavy production of proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. Interactions of the autonomic nervous system with local immune cells play an important role in the development of IBD, and the balance of autonomic nerve function is broken in IBD patients with sympathetic overactivity. However, the function of catecholamines in the progress of colitis is unclear. In this study, we examined the role of catecholamines via alpha 2-adrenoreceptor in acute murine colitis. The expression of tyrosine hydroxylase (TH) and dopamine b-hydroxylase (DBH), two rate-limiting enzymes in catecholamine synthesis, was detected by immunohistochemistry in murine colitis. Murine colitis was induced by dextran sodium sulphate or trinitrobenzene sulphonic acid (TNBS), and the mice were administered RX821002 or UK14304, alpha 2-adrenoceptor antagonists or agonists. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, TNF-alpha and IL-1 beta production and histology. Lamina propria mononuclear cells (LPMCs) from mice with TNBS colitis were cultured in the absence or presence of RX821002 or UK14304, and stimulated further by lipopolysaccharide. TH and DBH are induced in LPMCs of inflamed colon, the evidence of catecholamine synthesis during the process of colitis. RX821002 down-regulates the production of proinflammatory cytokines from LPMCs, while UK14304 leads to exacerbation of colitis. Together, our data show a critical role of catecholamines via alpha 2-adrenoreceptors in the progress of acute colitis, and suggest that use of the alpha 2-adrenoceptor antagonist represents a novel therapeutic approach for the management of colitis.