Önal Harika Topal, Yetkin Derya, Ayaz Furkan
Medical Laboratory Techniques, Vocational School of Health Services, Toros University, 33140 Mersin, Turkiye.
Advanced Technology Education Research and Application Center, Mersin University, Mersin 33110, Turkiye.
J Neuroimmunol. 2025 Feb 15;399:578514. doi: 10.1016/j.jneuroim.2024.578514. Epub 2024 Dec 14.
This study explores the nuanced immunomodulatory effects of sertraline, which is widely used in the treatment of major depression, obsessive-compulsive disorder, and anxiety in adults and children. Recent investigations have emphasized the intricate interplay between depression and the body's inflammatory response. This has sparked an exploration into the impact of sertraline on the immune system, an area that still awaits comprehensive exploration. Our research methodically examines the influence of sertraline on the levels of cytokines (TNF-a, IL-6, IL-12p40, GM-CSF) in the macrophage cell line J774.2. This analysis is conducted under conditions with and without the lipopolysaccharide (LPS) danger signal. To enhance specificity, sertraline's effects are juxtaposed with those of salicylic acid, a known anti-inflammatory agent. Furthermore, a comprehensive exploration of sertraline's impact on the intracellular signaling pathways regulated phosphoinositide-3-kinase (PI3K) and the p38 pathway is the third major signaling cassettes of the mitogen-activated protein kinase (MAPK) signaling is presented. The outcomes of our study unveil distinctive patterns in sertraline's modulation of cytokine levels within macrophage cells. Under the influence of the LPS danger signal, sertraline exhibits immunostimulatory characteristics, contrasting with its ability to suppress GM-CSF cytokine levels, even in the presence of LPS. Notably, the p38 pathway portrays a pro-inflammatory role for sertraline, while inhibiting the PI3K signaling pathway highlights its anti-inflammatory attributes. These findings contribute novel insights into the intricate interplay between sertraline and the immune system.
本研究探讨了舍曲林的细微免疫调节作用，该药物广泛用于治疗成人和儿童的重度抑郁症、强迫症和焦虑症。最近的研究强调了抑郁症与身体炎症反应之间的复杂相互作用。这引发了对舍曲林对免疫系统影响的探索，而这一领域仍有待全面研究。我们的研究系统地考察了舍曲林对巨噬细胞系J774.2中细胞因子（TNF-α、IL-6、IL-12p40、GM-CSF）水平的影响。该分析在有和没有脂多糖（LPS）危险信号的条件下进行。为了提高特异性，将舍曲林的作用与已知抗炎剂水杨酸的作用进行了对比。此外，还全面探讨了舍曲林对由磷酸肌醇-3-激酶（PI3K）和p38途径调节的细胞内信号通路的影响，这是丝裂原活化蛋白激酶（MAPK）信号的第三个主要信号盒。我们的研究结果揭示了舍曲林对巨噬细胞内细胞因子水平调节的独特模式。在LPS危险信号的影响下，舍曲林表现出免疫刺激特性，这与其即使在存在LPS的情况下抑制GM-CSF细胞因子水平的能力形成对比。值得注意的是，p38途径显示舍曲林具有促炎作用，而抑制PI3K信号通路则突出了其抗炎特性。这些发现为舍曲林与免疫系统之间的复杂相互作用提供了新的见解。
