β2-adrenoceptor signaling reduction in dendritic cells is involved in the inflammatory response in adjuvant-induced arthritic rats.
β2-adrenoceptor signaling reduction in dendritic cells is involved in the inflammatory response in adjuvant-induced arthritic rats.
复制标题
树突状细胞中β2-肾上腺素受体信号传导的减少参与佐剂诱导的关节炎大鼠的炎症反应
DOI：
10.1038/srep24548
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发表时间：
2016-04-15
影响因子：
4.6
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Wu H;Chen J;Song S;Yuan P;Liu L;Zhang Y;Zhou A;Chang Y;Zhang L;Wei W
类风湿性关节炎（RA）的特征是滑膜炎症，导致软骨和骨骼的进行性破坏。肾上腺素受体 (AR) 信号传导可能在调节树突状细胞 (DC) 中发挥重要作用，而树突状细胞可能参与 RA 的发病机制。我们研究了 β-AR 激动剂异丙肾上腺素 (ISO) 对 DC 功能的影响、β2-AR 激动剂沙丁胺醇对佐剂诱导的关节炎 (AA) 大鼠的影响，以及 AA 过程中 DC 中 β2-AR 信号传导的变化。 ISO抑制表面分子CD86和MHC-II的表达，抑制DC和TNF-α分泌刺激T淋巴细胞增殖，促进DC抗原摄取和IL-10分泌。 ISO 对 MHC-II 表达、DC 刺激 T 淋巴细胞增殖和 DC 抗原摄取的影响是由 β2-AR 介导的。沙丁胺醇治疗改善了 AA 的严重程度和关节的组织病理学，并抑制了体内胸腺淋巴细胞和 FLS 的增殖。与对照组相比，AA 大鼠的 β2-AR 信号传导较弱。在 AA 中观察到 DC 细胞膜中 GRK2 升高和 β2-AR 表达降低，这可能降低了 β2-AR 信号传导的抗炎作用。 β2-AR 信号传导减少可能与关节炎炎症的恶化有关。
Rheumatoid arthritis (RA) is characterized by inflammation of the synovium, which leads to the progressive destruction of cartilage and bone. Adrenoreceptor (AR) signaling may play an important role in modulating dendritic cell (DC), which may be involved in the pathogenesis of RA. We examined the effect of the β-AR agonist isoprenaline (ISO) on DC function, the impact of the β2-AR agonist salbutamol on adjuvant-induced arthritic (AA) rats, and changes in β2-AR signaling in DCs during the course of AA. ISO inhibited the expression of the surface molecules CD86 and MHC-II, inhibited the stimulation of T lymphocyte proliferation by DC and TNF-α secretion, and promoted DC antigen uptake and IL-10 secretion. The effects of ISO on MHC-II expression, DC stimulation of T lymphocyte proliferation, and DC antigen uptake were mediated by β2-AR. Treatment with salbutamol ameliorated the severity of AA and histopathology of the joints and inhibited proliferation of thymus lymphocytes and FLS in vivo. β2-AR signaling was weaker in AA rats compared to the control. Elevated GRK2 and decreased β2-AR expression in DC cytomembranes were observed in AA and may have decreased the anti-inflammatory effect of β2-AR signaling. Decreased β2-AR signaling may be relevant to the exacerbation of arthritis inflammation.