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.

中文翻译：

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薄荷醇是一种独特的尿液挥发性化合物，与间质性膀胱炎的慢性炎症有关。

慢性炎症是许多膀胱功能障碍的潜在全身危险因素，包括间质性膀胱炎（IC）。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 IC 患者和健康对照尿液中的气味化合物。利用综合固相微萃取-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 IC 患者尿液中挥发性代谢物（例如薄荷醇）的水平显着降低，与健康对照相比。为了了解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) 刺激炎症事件，例如炎症细胞因子（例如 TNF-α、IL-6 和 IL-1β）的产生和分泌以及 NF-κB 和相关蛋白的激活薄荷醇的存在会抑制大型信号网络（例如 Akt、TLR1、TNFAIP3 和 NF-κB）。这些发现拓宽了我们对尿薄荷醇在抑制炎症事件中作用的认识，并为减轻与 IC 相关的气味和炎症提供了潜在的新策略。