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.
摘要:
我们调查了28例克罗恩病(CD)患者的选择性氧化脂素和相关的合成/信号通路,19例溃疡性结肠炎(UC),39个控制通过LC-MS/MS分析血浆和粘膜PUFA/羟脂素谱。5、12和15-脂氧合酶的mRNA表达,FPR2/ALXR,通过qRT-PCR分析FFAR4/GPR120、膜联蛋白A1和白细胞介素-10。CD和UC患者的Oxylipin曲线和相关代谢途径均发生改变。这些模式的特征是前列腺素增加,白三烯,和脂氧素和5-脂氧合酶的过表达,FPR2/ALXR,膜联蛋白A1和白细胞介素-10基因,但减少n-3PUFA和18-羟基二十碳五烯酸。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衍生物以及有利于前者的促炎和抗炎/促解介质有关。研究结果表明,氧化脂素参与了疾病的病理生理学。靶向oxylipin的代谢途径将是一种有前途的治疗炎症性肠病。