Centro Di Riferimento Regionale Fibrosi Cistica, Naples, Italy.
Dipartimento Di Scienze Mediche Traslazionali, Università Di Napoli Federico II, Naples, Italy.
Sci Rep. 2022 Apr 7;12(1):5838. doi: 10.1038/s41598-022-09618-7.
Oxylipins are signaling molecules originated by fatty acids that modulate vascular and bronchial tone, bronchial secretion, cytokine production and immune cell activity. The unbalanced production of pro-inflammatory and pro-resolving (i.e., anti-inflammatory) oxylipins has a relevant role in the pathogenesis of pulmonary inflammation like in cystic fibrosis (CF). We analyzed by LC-MRM/MS 65 oxylipins and 4 fatty acids in resting saliva from 69 patients with CF and 50 healthy subjects (controls). The salivary levels of 48/65 oxylipins were significantly different between CF patients and controls. Among these, EpETE, DHET, 6ketoPGE1 and HDHA were significantly higher in saliva from CF patients than in controls. All these molecules display anti-inflammatory effects, i.e., releasing of bronchial and vascular tone, modulation of cytokine release. While 20-hydroxyPGF2A, PGB2, EpDPE, 9 K-12-ELA, bicyclo-PGE2, oleic acid, LTC4, linoleic acid, 15oxoEDE, 20 hydroxyPGE2 and DHK-PGD2/PGE2 (mostly associated to pro-inflammatory effects) resulted significantly lower in CF patients than in controls. Our data suggest that the salivary oxylipins profile in CF patients is addressed toward a global anti-inflammatory effect. Although these findings need be confirmed on larger populations in prospective studies, they will contribute to better understand the pathogenesis of CF chronic inflammation and to drive targeted therapies based on the modulation of oxylipins synthesis and degradation.
氧化脂类是由脂肪酸衍生而来的信号分子，可调节血管和支气管张力、支气管分泌、细胞因子产生和免疫细胞活性。促炎和促解决（即抗炎）氧化脂类的不平衡产生在肺部炎症的发病机制中具有重要作用，如囊性纤维化（CF）。我们通过 LC-MRM/MS 分析了 69 名 CF 患者和 50 名健康受试者（对照组）静息唾液中的 65 种氧化脂类和 4 种脂肪酸。CF 患者和对照组之间的 65 种氧化脂类中有 48 种的唾液水平存在显著差异。其中，EpETE、DHET、6ketoPGE1 和 HDHA 在 CF 患者的唾液中明显高于对照组。所有这些分子都具有抗炎作用，即释放支气管和血管张力、调节细胞因子释放。而 20-羟基 PG F2A、PGB2、EpDPE、9-K-12-ELA、双环 PG E2、油酸、LTC4、亚油酸、15oxoEDE、20 羟基 PG E2 和 DHK-PGD2/PGE2（主要与促炎作用相关）在 CF 患者中明显低于对照组。我们的数据表明，CF 患者的唾液氧化脂类谱偏向于整体抗炎作用。尽管这些发现需要在更大的前瞻性研究人群中得到证实，但它们将有助于更好地理解 CF 慢性炎症的发病机制，并基于氧化脂类合成和降解的调节来驱动靶向治疗。
