Neuronal α1/2-adrenergic stimulation of IFN-γ, IL-6, and CXCL-1 in murine spleen in late experimental arthritis
Neuronal α1/2-adrenergic stimulation of IFN-γ, IL-6, and CXCL-1 in murine spleen in late experimental arthritis
复制标题
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
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
R. Straub
中科院分区：
文献类型：
--
作者：
T. Meinel;G. Pongratz;L. Rauch;R. Straub
目的：在II型胶原诱导的关节炎（CIA）早期（32天），交感神经纤维和产生精氨酸的脾细胞之间存在功能性串扰。这些早期的实验证明了IFN-γ、CXCL 1、IL-6和TGF-β的唯一神经交感神经调节。然而，在晚期关节炎中，交感神经的影响可能会改变，由于交感神经纤维的损失和神经递质产生细胞的出现。方法：免疫后第58天（46-68天）取小鼠脾脏，制备0.35 mm厚的脾片，将其转移至灌流微室中，电诱导神经递质的释放。结果：电刺激可抑制IFN-γ、CXCL 1和IL-6的分泌，刺激TGF-β的分泌，但其作用远低于CIA早期。存在与电刺激无关的IFN-γ、IL-6和TGF-β的β肾上腺素能抑制（以及CXCL 1的刺激）（解释为非神经元）。结论：在CIA晚期，细胞因子分泌的非神经调节作用增强，而神经调节作用明显减弱。特别是，β-肾上腺素能效应是非神经元的，而α1/2-肾上腺素能效应明显是神经元的。我们认为，脾脏交感神经支配的改变从根本上改变了关节炎小鼠脾脏的功能性神经免疫相互作用。
Objective:Functional cross-talk exists between sympathetic nerve fibers and cytokine-producing splenic cells in early collagen type II–induced arthritis (CIA) (day 32). These earlier experiments demonstrated exclusively neuronal sympathetic regulation of IFN-γ, CXCL1, IL-6, and TGF-β. However, in late arthritis, the sympathetic influence might change due to loss of sympathetic nerve fibers and appearance of neurotransmitter-producing cells. We aimed to investigate neurotransmitter-dependent regulation of IFN-γ, CXCL1, IL-6, and TGF-β in murine spleen in late CIA.Methods:Spleens were removed when animals reached day 58 (46–68) after immunization to generate 0.35 mm-thick spleen slices, which were transferred to superfusion microchambers to electrically induce release of neurotransmitters. Using respective neurotransmitter antagonists, effects of released neurotransmitters on cytokine secretion were investigated.Results:There was electrically induced inhibition of IFN-γ, CXCL1, and IL-6, and stimulation of TGF-β, which was much less pronounced than in early CIA. There existed β adrenergic inhibition of IFN-γ, IL-6, and TGF-β (and stimulation of CXCL1) independent of electrical stimulation (interpreted as non-neuronal). However, there was a neuronal α1/2 adrenergic stimulation of IFN-γ, CXCL1, and IL-6 and, we observed neuronal A1-adenosinergic stimulation of TGF-β.Conclusions:In the late phase of CIA, non-neuronal modulation of cytokine secretion increases while neuronal regulation strikingly decreases. Particularly, β-adrenergic effects are non-neuronal while α1/2-adrenergic effects are clearly neuronal. We suggest that alterations in sympathetic innervation of the spleen fundamentally change the functional neuroimmune interplay in the spleen of arthritic mice.
影响因子：
56.9
作者：
Luttrell, LM;Ferguson, SSG;Lefkowitz, RJ
通讯作者：
Lefkowitz, RJ