Abnormal expression of oxylipins and related synthesizing/signaling pathways in inflammatory bowel diseases

IF 3 Prostaglandins, leukotrienes, and essential fatty acids Pub Date : 2024-03-01 DOI:10.1016/j.plefa.2024.102628

Yamina Ben-Mustapha , Raja Rekik , Mohamed K. Ben-Fradj , Meriem Serghini , Haifa Sanhaji , Melika Ben-Ahmed , Jalel Boubaker , Moncef Feki

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Abstract

We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases.

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炎症性肠病中草脂素及相关合成/信号通路的异常表达。

我们研究了 28 名克罗恩病（CD）患者、19 名溃疡性结肠炎（UC）患者和 39 名对照组患者体内的部分氧脂和相关合成/信号通路。通过 qRT-PCR 分析了 5、12 和 15-脂氧合酶、FPR2/ALXR、FFAR4/GPR120、附件素 A1 和白细胞介素-10 的 mRNA 表达。在 CD 和 UC 患者中，氧脂代谢概况和相关代谢途径都发生了改变。其特点是前列腺素、白三烯和脂毒素增加，5-脂氧合酶、FPR2/ALXR、附件素 A1 和白细胞介素-10 基因过度表达，但 n-3 PUFAs 和 18-hydroxyeisapentaenoic acid 减少。15-脂氧合酶基因主要在 UC 患者中表达不足。CD 和 UC 与不平衡的 n-6 和 n-3 衍生物以及促炎和抗炎/消炎介质有关，前者更受青睐。研究结果表明，氧脂素参与了这些疾病的病理生理学。以氧脂代谢途径为靶点将是一种治疗炎症性肠病的有效方法。

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