Sympathetic nervous modulation of the skin innate and adaptive immune response to peptidoglycan but not lipopolysaccharide:: Involvement of β-adrenoceptors and relevance in inflammatory diseases
Sympathetic nervous modulation of the skin innate and adaptive immune response to peptidoglycan but not lipopolysaccharide:: Involvement of β-adrenoceptors and relevance in inflammatory diseases
复制标题
DOI：
10.1016/j.bbi.2007.06.016
复制
发表时间：
2008-01-01
影响因子：
15.1
通讯作者：
Maestroni, Georges J. M.
中科院分区：
文献类型：
--
作者：
Manni, Michela;Maestroni, Georges J. M.
皮肤免疫活性的紊乱与获得性炎性皮肤病的发病机制有关。包括银屑病、特应性皮炎、扁平苔藓和白癜风在内的炎症性疾病也与肾上腺素能机制和情绪应激的局部改变有关。在这里，我们表明，β-肾上腺素能受体拮抗剂普萘洛尔沿着与肽聚糖，但不是LPS，结合皮内注射的可溶性蛋白质，转移的回忆记忆反应的Th 1型。特异性β 2-AR拮抗剂ICI 118，551没有再现这种效应，表明β 1-和β 2-AR的抑制引起Th 1极化。潜在的机制包括在应答的先天期期间IFN-γ、IL-12和IL-23以及IFN-β和CXCR 3配体的局部表达增强，这导致引流淋巴结中抗原阳性浆细胞样树突状细胞（pDC）的增加。特别是，炎症细胞因子和IFN-β诱导基因表达的调节似乎也涉及β 1-AR。最近有报道称，浆细胞样树突状细胞和IL-23在银屑病等Th 1持续性炎症性皮肤病的发病机制中发挥核心作用。因此，原发性β-肾上腺素受体信号传导缺陷或交感神经活性改变以及选定的模式识别受体激活可能作为许多Th 1持续性炎症性皮肤病的起始和/或持续因素。(C)2007爱思唯尔公司All rights reserved.
Disorders of the skin immune activity are implicated in the pathogenesis of acquired inflammatory skin disorders. Inflammatory diseases including psoriasis, atopic dermatitis, lichen planus and vitiligo have also been associated with local alterations of adrenergic mechanisms and emotional stress. Here we show that the beta-adrenergic receptors antagonist propranolol along with peptidoglycan, but not LPS, combined with intradermal injection of a soluble protein, shifted the recall memory response to the Th 1 type. The specific beta 2-AR antagonist ICI 118,551 did not reproduce this effect suggesting that inhibition of both beta 1- and beta 2-AR caused the Th1 polarization. The underlying mechanism included enhanced local expression of IFN-gamma, IL-12 and IL-23 as well as of IFN-beta and CXCR3 ligands during the innate phase of the response which resulted in an increase of antigen-positive plasmacytoid dendritic cells (pDCs) in the draining lymph node. In particular, modulation of inflammatory cytokines, and IFN-beta inducible genes expression appeared to involve also the beta 1-AR. Plasmacytoid dendritic cells and IL-23 were recently reported to play a central role in the pathogenesis of Th1-sustained inflammatory skin diseases such as psoriasis. Thus, primary beta-adrenoceptors signaling defects or altered sympathetic nervous activity together with selected pattern recognition receptors activation might serve as initiation and/or persistence factors for numerous Th1-sustained inflammatory skin diseases. (C) 2007 Elsevier Inc. All rights reserved.