Adrenergic and glucocorticoid modulation of the sterile inflammatory response
Adrenergic and glucocorticoid modulation of the sterile inflammatory response
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DOI：
10.1016/j.bbi.2013.11.018
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发表时间：
2014-02-01
影响因子：
15.1
通讯作者：
Fleshner, Monika
中科院分区：
文献类型：
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作者：
Cox, Stewart S.;Speaker, Kristin J.;Fleshner, Monika
在没有病原体的情况下，暴露于强烈的急性应激源会改变免疫功能。暴露于一次不可避免的尾电击会增加血浆和组织中细胞因子、趋化因子和危险相关分子模式（DAMP） Hsp72的浓度。虽然先前的研究已经证明肾上腺素能受体（ADR）和糖皮质激素受体（GCR）介导的途径改变病原体或微生物相关分子模式（MAMP）诱发的细胞因子、趋化因子和Hsp72水平，但很少有研究测试这些受体在多种炎症蛋白或组织中的作用，以阐明应激诱发的无菌炎症反应的大小差异。本研究的目的是：(1)通过测量细胞因子、趋化因子和DAMP （Hsp72）反应，比较循环、肝脏、脾脏和皮下（SQ）脂肪组织中的无菌炎症反应；(2)测试α -1 （α(1)）、β -1 （β(1)）、β -2 （β(2)）和β -3 （β(3)）不良反应以及gcr在无菌炎症反应信号传导中的作用。所提供的数据表明，血浆和SQ脂肪明显比肝脏和脾脏更具有应激反应性。此外，ADR和gcr特异性拮抗剂的使用揭示了所研究组织中无菌炎症反应的信号机制的相似性和差异性。最后，考虑到SQ组织中趋化因子单核细胞趋化蛋白-1 （MCP-1）的选择性增加，SQ脂肪可能是白细胞迁移的重要部位，可能是为受伤后的感染做准备。本研究有助于进一步了解应激性无菌炎症反应的组织特异性差异。(C) 2013爱思唯尔公司版权所有。
Exposure to an intense, acute stressor, in the absence of a pathogen, alters immune function. Exposure to a single bout of inescapable tail shock increases plasma and tissue concentrations of cytokines, chemokines, and the danger associated molecular pattern (DAMP) Hsp72. Although previous studies have demonstrated that adrenergic receptor (ADR) and glucocorticoid receptor (GCR)-mediated pathways alter pathogen or microbial associated molecular pattern (MAMP)-evoked levels of cytokines, chemokines, and Hsp72, far fewer studies have tested the role of these receptors across multiple inflammatory proteins or tissues to elucidate the differences in magnitude of stress-evoked sterile inflammatory responses. The goals of the current study were to (1) compare the sterile inflammatory response in the circulation, liver, spleen, and subcutaneous (SQ) adipose tissue by measuring cytokine, chemokine, and DAMP (Hsp72) responses; and (2) to test the role of alpha-1 (alpha(1)), beta-1 (beta(1)), beta-2 (beta(2)), and beta-3 (beta(3)) ADRs, as well as GCRs in signaling the sterile inflammatory response. The data presented indicate plasma and SQ adipose are significantly more stress responsive than the liver and spleen. Further, administration of ADR and GCR-specific antagonists revealed both similarities and differences in the signaling mechanisms of the sterile inflammatory response in the tissues studied. Finally, given the selective increase in the chemokine monocyte chemotactic protein-1 (MCP-1) in SQ tissue, it may be that SQ adipose is an important site of leukocyte migration, possibly in preparation for infection as a consequence of wounding. The current study helps further our understanding of the tissue-specific differences of the stress-induced sterile inflammatory response. (C) 2013 Elsevier Inc. All rights reserved.