Department of Medical, Oral and Biotechnological Science, University "G. d'Annunzio" Chieti- Pescara, 66100 Chieti, Italy.
Center of Sleep Medicine, Department of Neurology, Villa Serena Hospital, Città S. Angelo, 65013 Pescara, Italy.
Int J Mol Sci. 2020 May 5;21(9):3264. doi: 10.3390/ijms21093264.
The role of inflammation and dysfunction of the cholinergic system in obstructive sleep apnea (OSA) has not exhaustively clarified. Thus, in this study, we explore the non-neuronal cholinergic system and the balance of T helper (Th) 17- and T regulatory (Treg)-related cytokines in OSA patients. The study includes 33 subjects with obstructive sleep apnea and 10 healthy controls (HC). The expression levels of cholinergic system component, RAR-related orphan receptor (RORc), transcription factor forkhead box protein 3 (Foxp3) and cytokines were evaluated. Th17- and Treg-related cytokines, choline levels and acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activity were quantified in OSA and control subjects. AChE and nicotinic receptor α 7 subunit (α7nAChR) gene expression and serum levels of choline, AChE and BuChE were lower in OSA patients than in the HC group. Compared with the HC group, OSA patients exhibited an increased expression, secretion and serum levels of pro-inflammatory cytokines, a reduced expression, secretion and serum levels of transforming growth factor (TGF)β and reduced Foxp3 mRNA levels. The Th17/Treg-related cytokine ratio was higher in the OSA group. Our results confirm and reinforce the hypothesis that OSA may be considered a systemic inflammatory disease, and that an imbalance of non-neuronal cholinergic and pro/anti-inflammatory cytokines may contribute to development and progression of comorbidities in OSA subjects. The evaluation of Th17/Treg-related cytokine may provide an additional explanation for OSA pathogenesis and clinical features, opening new directions for the OSA management.
炎症和胆碱能系统功能障碍在阻塞性睡眠呼吸暂停（OSA）中的作用尚未完全阐明。因此，在这项研究中，我们探讨了非神经胆碱能系统以及 OSA 患者中辅助性 T 细胞（Th）17 和调节性 T 细胞（Treg）相关细胞因子的平衡。该研究纳入了 33 例阻塞性睡眠呼吸暂停患者和 10 名健康对照者（HC）。评估了胆碱能系统成分、维甲酸相关孤儿受体（RORc）、叉头框蛋白 3（Foxp3）和细胞因子的表达水平。定量检测了 OSA 和对照组患者的 Th17 和 Treg 相关细胞因子、胆碱水平和乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BuChE）活性。与 HC 组相比，OSA 患者的 AChE 和烟碱型乙酰胆碱受体α7 亚单位（α7nAChR）基因表达以及血清胆碱、AChE 和 BuChE 水平均较低。与 HC 组相比，OSA 患者表现出促炎细胞因子的表达、分泌和血清水平增加，转化生长因子（TGF）β的表达、分泌和血清水平降低，Foxp3 mRNA 水平降低。OSA 组 Th17/Treg 相关细胞因子比值较高。我们的研究结果证实并强化了 OSA 可能被视为一种系统性炎症性疾病的假说，并且非神经胆碱能和促炎/抗炎细胞因子的失衡可能导致 OSA 患者合并症的发生和发展。Th17/Treg 相关细胞因子的评估可能为 OSA 发病机制和临床特征提供额外的解释，为 OSA 的管理开辟了新的方向。
