Proinflammatory α-Adrenergic Neuronal Regulation of Splenic IFN-γ, IL-6, and TGF-β of Mice from Day 15 onwards in Arthritis
Proinflammatory α-Adrenergic Neuronal Regulation of Splenic IFN-γ, IL-6, and TGF-β of Mice from Day 15 onwards in Arthritis
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从关节炎第 15 天起，小鼠脾脏 IFN-γ、IL-6 和 TGF-β 的促炎 α-肾上腺素能神经元调节
DOI：
10.1159/000508109
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发表时间：
2020
影响因子：
2.4
通讯作者：
Rauch L
中科院分区：
文献类型：
--
作者：
Straub RH;Dufner B;Rauch L
在关节炎小鼠中，交感神经的影响是从免疫时间点到疾病发作（0-32天）的促炎性，但原因尚不清楚。通过G α s偶联受体破坏主要抗炎途径可能起作用。例如，去甲肾上腺素不能通过抗炎β 2-肾上腺素受体起作用，而是通过促炎α 1/2-肾上腺素受体起作用。这可能首先是由于炎症组织中交感神经纤维的丧失，神经递质水平较低（去甲肾上腺素只与高亲和力的α-肾上腺素受体结合），其次是由于G蛋白受体偶联的改变，α-肾上腺素能信号占优势。我们假设，这两种机制发挥作用的过程中，胶原蛋白II型诱导的关节炎（CIA）在脾脏中的mice.MethodsIn CIA小鼠，在脾脏中的神经纤维密度定量免疫组织化学技术。通过脾切片的微灌注技术研究了脾交感神经纤维的功能影响，重点是IFN-γ和IL-6（促炎）和TGF-β（抗炎）的分泌。电释放的去甲肾上腺素的影响在关节炎的过程中减少。在所有研究的时间点（第14，32和55天），只有促炎神经元α-肾上腺素能细胞因子分泌的影响被证明（即，刺激IFN-γ和IL-6和抑制TGF-β）。这些结果支持关节炎中促炎性α-肾上腺素能交感神经影响的优势。
IntroductionIn arthritic mice, a sympathetic influence is proinflammatory from the time point of immunization until the onset of disease (days 0–32), but reasons are unknown. Disruption of the major anti-inflammatory pathway through G αs-coupled receptors probably play a role. For example, noradrenaline cannot operate via anti-inflammatory β 2-adrenoceptors but through proinflammatory α 1/2-ad-renoceptors. This might happen, first, through a loss of sympathetic nerve fibers in inflamed tissue with low neurotransmitter levels (noradrenaline only binds to high-affinity α-adrenoceptors) and, second, through an alteration in G-protein receptor coupling with a predominance of α-adrenergic signaling. We hypothesized that both mechanisms play a role in the course of collagen type II-induced arthritis (CIA) in the spleen in mice.MethodsIn CIA mice, nerve fiber density in the spleen was quantified by immunohistochemistry techniques. The functional impact of sympathetic nerve fibers in the spleen was studied by a micro-superfusion technique of spleen slices with a focus on the secretion of IFN-γ and IL-6 (proinflammatory) and TGF-β (anti-inflammatory).ResultsDuring CIA, sympathetic nerve fibers get increasingly lost from day14 until day 55 after immunization. The influence of electrically released noradrenaline diminishes in the course of arthritis. At all investigated time points (days 14, 32, and 55), only proinflammatory neuronal α-adrenergic effects on cytokine secretion were demonstrated (ie, stimulation of IFN-γ and IL-6 and inhibition of TGF-β).ConclusionSympathetic nerve fibers are rapidly lost in the spleen, and only proinflammatory α-adrenergic neuronal regulation of cytokine secretion takes place throughout the course of arthritis. These results support a predominance of a proinflammatory α-adrenergic sympathetic influence in arthritis.
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影响因子：
15.1
作者：
Straub, Rainer H.;Rauch, Luise;Pongratz, Georg
通讯作者：
Pongratz, Georg
晚期实验性关节炎小鼠脾脏中 IFN-γ、IL-6 和 CXCL-1 的神经元 α1/2-肾上腺素刺激
DOI：
10.1016/j.bbi.2013.06.003
发表时间：
2013
期刊：
Brain, Behavior, and Immunity
影响因子：
--
作者：
T. Meinel;G. Pongratz;L. Rauch;R. Straub
通讯作者：
R. Straub
影响因子：
15.1
作者：
Klatt, Susanne;Stangl, Hubert;Straub, Rainer H.
通讯作者：
Straub, Rainer H.
体外灌注法研究小鼠脾脏神经免疫细胞相互作用
影响因子：
3.3
作者：
R. Straub;B. Lang;W. Falk;J. Schölmerich;E. Singer
通讯作者：
E. Singer
影响因子：
4.4
作者：
R. Spengler;S. Chensue;D. Giacherio;Nicole Blenk;S. Kunkel
通讯作者：
R. Spengler;S. Chensue;D. Giacherio;Nicole Blenk;S. Kunkel