Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Institute for Systems Biology, Seattle, WA, USA.
Sci Rep. 2018 Jul 18;8(1):10859. doi: 10.1038/s41598-018-29085-3.
Chronic inflammation is a potential systemic risk factor for many bladder dysfunctions, including interstitial cystitis (IC). However, the underlying mechanism through which a healthy bladder protects itself from inflammatory triggers remains unknown. In this study, we identified odor compounds in urine obtained from IC patients and healthy controls. Using comprehensive solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (SPME-GC-TOF-MS) profiling and bioinformatics, we found that levels of urinary volatile metabolites, such as menthol, were significantly reduced in IC patients, compared to healthy controls. In an attempt to understand the mechanistic meaning of our volatile metabolites data and the role of menthol in the immune system, we performed two independent experiments: (a) cytokine profiling, and (b) DNA microarray. Our findings suggest that lipopolysaccharide (LPS)-stimulated inflammatory events, such as the production and secretion of inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β) and the activation of NF-κB and associated proteins within a large signaling network (e.g., Akt, TLR1, TNFAIP3, and NF-κB), are suppressed by the presence of menthol. These findings broaden our knowledge on the role of urinary menthol in suppressing inflammatory events and provide potential new strategies for alleviating both the odor and inflammation associated with IC.
慢性炎症是许多膀胱功能障碍（包括间质性膀胱炎）的潜在全身性危险因素。然而，健康膀胱保护自身免受炎症触发的潜在机制仍不清楚。在这项研究中，我们鉴定了来自间质性膀胱炎患者和健康对照者尿液中的气味化合物。使用全面的固相微萃取-气相色谱-飞行时间质谱（SPME-GC-TOF-MS）分析和生物信息学，我们发现间质性膀胱炎患者尿液中挥发性代谢物（如薄荷醇）的水平明显低于健康对照组。为了了解我们的挥发性代谢物数据的机制意义以及薄荷醇在免疫系统中的作用，我们进行了两项独立的实验：（a）细胞因子分析，和（b）DNA 微阵列。我们的研究结果表明，脂多糖（LPS）刺激的炎症事件，如炎症细胞因子（如 TNF-α、IL-6 和 IL-1β）的产生和分泌以及 NF-κB 和相关蛋白（如 Akt、TLR1、TNFAIP3 和 NF-κB）在一个大型信号网络中的激活，受到薄荷醇的抑制。这些发现拓宽了我们对尿液中薄荷醇在抑制炎症事件中的作用的认识，并为缓解与间质性膀胱炎相关的气味和炎症提供了潜在的新策略。
